Publications by authors named "Lawless C"

Mitochondria play a crucial role in maintaining cellular health. It is interesting that the shape of mitochondria can vary depending on the type of cell, mitochondrial function, and other cellular conditions. However, there are limited studies that link functional assessment with mitochondrial morphology evaluation at high magnification, even fewer that do so in situ and none in human muscle biopsies.

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Chemical signaling can play a crucial role in predator-prey dynamics. Here, we present evidence that ink from the common cuttlefish (Sepia officinalis) targets olfactory receptor proteins in shark, potentially acting as a predator deterrence. We apply in silico 3D docking analysis to investigate the binding affinity of various odorant molecules to shark olfactory receptors of two shark species: cloudy catshark (Scyliorhinus torazame) and white shark (Carcharodon carcharias).

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Zymoseptoria tritici is an ascomycete fungus and the causal agent of Septoria tritici leaf blotch (STB) in wheat. Z. tritici secretes an array of effector proteins that are likely to facilitate host infection, colonisation and pycnidia production.

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Kidney physiology shows diurnal variation, and a disrupted circadian rhythm is associated with kidney disease. However, it remains largely unknown whether glomeruli, the filtering units in the kidney, are under circadian control. Here, we investigated core circadian clock components in glomeruli, together with their rhythmic targets and modes of regulation.

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The mammalian retina contains high amounts of metals/metalloid-selenium. Their dyshomeostases are associated with certain retinal diseases. We carried out this bioinformatics study to identify the relationships between putative retinal metal/selenium binding proteins, their molecular functions, and biological processes.

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Heteroplasmic mitochondrial DNA (mtDNA) variants accumulate as humans age, particularly in the stem-cell compartments, and are an important contributor to age-related disease. Mitochondrial dysfunction has been observed in osteoporosis and somatic mtDNA pathogenic variants have been observed in animal models of osteoporosis. However, this has never been assessed in the relevant human tissue.

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Telehealth services are increasingly utilized to improve mental health care access for active-duty service members (ADSM) and military veterans. This article examines mental health outcomes for veterans ( = 4,536) and ADSMs ( = 378) who met diagnostic criteria for depression, posttraumatic stress disorder, or generalized anxiety disorder ( = 4,914) and were treated at Cohen Veterans Network Clinics using either telehealth or in-person treatment modalities. Results demonstrate small but statistically significant advantages for telehealth in terms of discharge scores, rates of clinically significant change, and efficiency of treatment.

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Three-dimensional (3D) organoid models have been instrumental in understanding molecular mechanisms responsible for many cellular processes and diseases. However, established organic biomaterial scaffolds used for 3D hydrogel cultures, such as Matrigel, are biochemically complex and display significant batch variability, limiting reproducibility in experiments. Recently, there has been significant progress in the development of synthetic hydrogels for in vitro cell culture that are reproducible, mechanically tuneable, and biocompatible.

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Mitochondrial DNA (mtDNA) deletions which clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impair mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these mtDNA deletions arise and accumulate in perinuclear mitochondria causing localised mitochondrial dysfunction before spreading through the muscle fibre. We believe that mito-nuclear signalling is a key contributor in the accumulation and spread of mtDNA deletions, and that knowledge of how muscle fibres respond to mitochondrial dysfunction is key to our understanding of disease mechanisms.

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Article Synopsis
  • The study investigates the genetic and brain features linked to vocal learning in mammals by comparing data from the Egyptian fruit bat and 215 other placental mammals.* -
  • Researchers found that certain proteins evolve more slowly in vocal learners and identified a specific brain region responsible for vocal motor control in the Egyptian fruit bat.* -
  • Using machine learning, they uncovered 50 regulatory elements that are associated with vocal learning, suggesting that losses in these elements played a role in the evolution of vocal learning in mammals.*
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Desmosomes are multiprotein adhesion complexes that link intermediate filaments to the plasma membrane, ensuring the mechanical integrity of cells across tissues, but how they participate in the wider signaling network to exert their full function is unclear. To investigate this, we carried out protein proximity mapping using biotinylation (BioID). The combined interactomes of the essential desmosomal proteins desmocollin 2a, plakoglobin, and plakophilin 2a (Pkp2a) in Madin-Darby canine kidney epithelial cells were mapped and their differences and commonalities characterized as desmosome matured from Ca dependence to the mature, Ca-independent, hyper-adhesive state, which predominates in tissues.

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Becker muscular dystrophy (BMD) is characterised by fiber loss and expansion of fibrotic and adipose tissue. Several cells interact locally in what is known as the degenerative niche. We analysed muscle biopsies of controls and BMD patients at early, moderate and advanced stages of progression using Hyperion imaging mass cytometry (IMC) by labelling single sections with 17 markers identifying different components of the muscle.

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Background: The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment.

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Summary: Sensory receptor gene families have undergone extensive expansion and loss across vertebrate evolution, leading to significant variation in receptor counts between species. However, due to their species-specific nature, conventional reference-based annotation tools often underestimate the true number of sensory receptors in a given species. While there has been an exponential increase in the taxonomic diversity of publicly available genome assemblies in recent years, only ∼30% of vertebrate species on the NCBI database are currently annotated.

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Basement membranes are specialized extracellular matrices formed by highly insoluble structural proteins and extracellular matrix (ECM)-bound components that provide structural and signaling support to tissues and are dynamic during development. Here, we present a mass spectrometry-based label-free quantitative proteomics protocol to investigate basement membranes and define their composition using samples from human kidney organoids and mouse fetal kidneys. This protocol facilitates the study of basement membrane and other ECM components during development to improve our understanding of matrix regulation and function.

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Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding).

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Chemokine-driven leukocyte recruitment is a key component of the immune response and of various diseases. Therapeutically targeting the chemokine system in inflammatory disease has been unsuccessful, which has been attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies.

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The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability.

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Article Synopsis
  • Pathogenic mitochondrial DNA (mtDNA) variants are a frequent cause of mitochondrial diseases in adults, and their levels in blood decrease with age due to different metabolic needs among blood cell types.* -
  • A study involving cell-sorting and mtDNA sequencing found that T cells show a greater decline in these variants compared to other blood cells, driven by their ability to eliminate mutated mtDNA as they differentiate.* -
  • Compared to healthy controls, patients with these mtDNA variants have fewer T cells, highlighting the importance of mitochondrial function for maintaining T cell levels and differentiation status in the blood.*
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Background: Myotonic dystrophy type 1 (DM1) is a dominant autosomal neuromuscular disorder caused by the inheritance of a CTG triplet repeat expansion in the Dystrophia Myotonica Protein Kinase (DMPK) gene. At present, no cure currently exists for DM1 disease.

Objective: This study investigates the effects of 12-week resistance exercise training on mitochondrial oxidative phosphorylation in skeletal muscle in a cohort of DM1 patients (n = 11, men) in comparison to control muscle with normal oxidative phosphorylation.

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Collagen is a key structural component of multicellular organisms and is arranged in a highly organized manner. In structural tissues such as tendons, collagen forms bundles of parallel fibers between cells, which appear within a 24-h window between embryonic day 13.5 (E13.

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Endocytic recycling controls the return of internalised cargoes to the plasma membrane to coordinate their positioning, availability and downstream signalling. The Rab4 and Rab11 small GTPase families regulate distinct recycling routes, broadly classified as fast recycling from early endosomes (Rab4) and slow recycling from perinuclear recycling endosomes (Rab11), and both routes handle a broad range of overlapping cargoes to regulate cell behaviour. We adopted a proximity labelling approach, BioID, to identify and compare the protein complexes recruited by Rab4a, Rab11a and Rab25 (a Rab11 family member implicated in cancer aggressiveness), revealing statistically robust protein-protein interaction networks of both new and well-characterised cargoes and trafficking machinery in migratory cancer cells.

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Article Synopsis
  • Zoonomia is the largest resource for studying mammalian genomes, analyzing 240 species to find genetic mutations that could impact fitness and disease risk.
  • Around 332 million bases in the human genome are highly conserved across species, indicating evolutionary significance, with 4552 of these being ultraconserved.
  • The research highlights that most constrained bases are outside protein-coding regions and not annotated, revealing potential insights for understanding unique traits in mammals and informing medical research.
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