Publications by authors named "Dougan C"

Mesenchymal stromal cells (MSCs) are multipotent adult stem cells which possess immunomodulatory and repair capabilities. In this study, we investigated whether MSC therapy could modulate inflammation and lung damage in the lungs of Scnn1b-transgenic mice overexpressing the β-subunit of the epithelial sodium channel (β-ENaC), a model with features of Cystic Fibrosis lung disease. Human bone marrow derived MSC cells were intravenously delivered to mice, prior to collection of bronchoalveolar lavage (BALF) and tissue.

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  • - SLPI is a key protein that plays a role in airway immunity by inhibiting harmful enzymatic activity, and it also has anti-inflammatory effects by regulating immune responses through NF-κB inhibition.
  • - In lung diseases like COPD and Cystic Fibrosis, SLPI levels can be elevated due to inflammation, but some studies show that COPD patients may have lower SLPI levels, which could weaken airway immunity.
  • - Researchers are using a mouse model that mimics features of COPD and CF to study the effects of SLPI by creating a genetically modified mouse (ENaC-Tg/SLPI) to understand how the absence of SLPI influences the progression of these chronic lung diseases.
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Traditional mechanical characterization of extremely soft tissues is challenging given difficulty extracting tissue, satisfying geometric requirements, keeping tissues hydrated, and securing the tissue in an apparatus without slippage. The heterogeneous nature and structural complexity of brain tissues on small length scales makes it especially difficult to characterize. Needle-induced cavitation (NIC) is a technique that overcomes these issues and can mechanically characterize brain tissues at precise, micrometer-scale locations.

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  • Traumatic brain injury (TBI) contributes to the risk of neurodegenerative diseases, but the link between acute TBI and ongoing brain degeneration remains poorly understood.
  • A novel technique called needle-induced cavitation (NIC) was used on mouse brain slices to model TBI, focusing on the hippocampus, which is crucial for learning and memory and is susceptible to cognitive impairments.
  • Combining NIC with electrophysiology revealed that this technique affects synaptic release in specific neurons and promotes neural repair through an extracellular matrix protein, providing insights for future research on TBI's impact and potential treatments.
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  • Traumatic brain injury (TBI) is linked to neurodegenerative diseases, but current understanding relies mostly on post-mortem studies with limited connections to injury dynamics and their cellular impacts.
  • Needle-induced cavitation (NIC) is used to create small bubbles in brain tissue, allowing researchers to study the effects of TBI on living mouse brain slices, specifically targeting the hippocampus, a region crucial for learning and memory.
  • The study shows that NIC alters synaptic function in the hippocampus and increases neural repair proteins, with these effects influenced by cannabinoid receptors, offering insights for future treatments targeting brain injury recovery.
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The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that match the ECM composition and biomechanics of the lung to study these cell-matrix interactions in vitro.

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The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that contain the ECM composition and biomechanics of the lung to study these cell-matrix interactions .

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Nonpenetrating traumatic brain injuries (TBIs) are linked to cavitation. The structural organization of the brain makes it particularly susceptible to tears and fractures from these cavitation events, but limitations in existing characterization methods make it difficult to understand the relationship between fracture and cavitation in this tissue. More broadly, fracture energy is an important, yet often overlooked, mechanical property of all soft tissues.

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Degradation of agrochemicals in soil is frequently faster under field conditions than in laboratory studies. Field studies are carried out on relatively undisturbed soil, whereas laboratory studies typically use sieved soil, which can have a significant impact on the physical and microbial nature of the soil and may contribute to differences in degradation between laboratory and field studies. A laboratory study was therefore conducted to determine the importance of soil structure and variable soil moisture on the degradation of 2 fungicides (azoxystrobin and paclobutrazol) that show significant differences between laboratory and field degradation rates in regulatory studies.

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Background: In the Twin Birth Study, women at 32-38 weeks of gestation, in whom the first twin was in cephalic presentation, were randomized to planned vaginal delivery or cesarean section. The study found no significant differences in neonatal or maternal outcomes in the two planned mode of delivery groups. We aimed to compare neonatal and maternal outcomes of twin gestations without spontaneous onset of labor, who underwent induction of labor or pre-labor cesarean section as the intervention of induction may affect outcomes.

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Characterizing the high-strain-rate and high-strain mechanics of soft materials is critical to understanding the complex behavior of polymers and various dynamic injury mechanisms, including traumatic brain injury. However, their dynamic mechanical deformation under extreme conditions is technically difficult to quantify and often includes irreversible damage. To address such challenges, we investigate an experimental method, which allows quantification of the extreme mechanical properties of soft materials using ultrafast stroboscopic imaging of highly reproducible laser-induced cavitation events.

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The whitespotted eagle ray Aetobatus narinari is a tropical to warm-temperate benthopelagic batoid that ranges widely throughout the western Atlantic Ocean. Despite conservation concerns for the species, its vertical habitat use and diving behaviour remain unknown. Patterns and drivers in the depth distribution of A.

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Cavitation is the sudden, unstable expansion of a void or bubble within a liquid or solid subjected to a negative hydrostatic stress. Cavitation rheology is a field emerging from the development of a suite of materials characterization, damage quantification, and therapeutic techniques that exploit the physical principles of cavitation. Cavitation rheology is inherently complex and broad in scope with wide-ranging applications in the biology, chemistry, materials, and mechanics communities.

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  • Multiple sclerosis (MS) is an autoimmune disorder affecting the central nervous system, primarily driven by harmful Th17 cells that produce inflammatory signals.
  • Research indicates that let-7 miRNAs can protect against MS by inhibiting the growth and movement of these damaging Th17 cells into the central nervous system.
  • This study highlights the potential of let-7 miRNAs as a therapeutic target for treating conditions related to MS by regulating Th17 cell differentiation.
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Empowering patients and working collaboratively to improve healthcare is a focus for current healthcare development strategies. In obstetric practice, working in collaboration with women to discuss mode of delivery after caesarean section has been shown to impact women's choice. A preliminary survey in our tertiary maternity unit showed 20% of women gained 'full clarity' with the information they received after caesarean-section regarding indication, complications and impact on future delivery.

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Cathepsin S (CatS) is upregulated in the lungs of patients with cystic fibrosis (CF). However, its role in CF lung disease pathogenesis remains unclear.In this study, β-epithelial Na channel-overexpressing transgenic (βENaC-Tg) mice, a model of CF-like lung disease, were crossed with CatS null (CatS) mice or treated with the CatS inhibitor VBY-999.

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Published data on the mechanical strength and elasticity of lung tissue is widely variable, primarily due to differences in how testing was conducted across individual studies. This makes it extremely difficult to find a benchmark modulus of lung tissue when designing synthetic extracellular matrices (ECMs). To address this issue, we tested tissues from various areas of the lung using multiple characterization techniques, including micro-indentation, small amplitude oscillatory shear (SAOS), uniaxial tension, and cavitation rheology.

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Background: The route and rate of degradation of thiamethoxam in the laboratory and field was investigated. The effect of dark incubation versus light/dark cycles, seed treatment versus spray, and watering-in for spray application was explored in side-by-side trials.

Results: Geometric mean DT values were 75.

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Background: The Twin Birth Study, a multicenter randomized controlled trial, found no differences in neonatal outcomes in women with twins randomized to planned cesarean or vaginal delivery. Nevertheless, women who present in spontaneous labor might expect a better outcome following a trial of vaginal delivery than undergoing cesarean delivery. In this secondary analysis, we aimed to compare neonatal outcomes of women who presented in spontaneous labor in the two arms of the Twin Birth Study.

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Members of the whey acidic protein (WAP) or WAP four-disulfide-core (WFDC) family of proteins are a relatively under-explored family of low molecular weight proteins. The two most prominent WFDC proteins, secretory leukocyte protease inhibitor (SLPI) and elafin (or the precursor, trappin-2), have been shown to possess multiple functions including anti-protease, anti-bacterial, anti-viral and anti-inflammatory properties. It is therefore of no surprise that both SLPI and elafin/trappin-2 have been developed as potential therapeutics.

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Development of anti-cancer drugs towards clinical application is costly and inefficient. Large screens of drugs, efficacious for non-cancer disease, are currently being used to identify candidates for repurposing based on their anti-cancer properties. Here, we show that low-dose salinomycin, a coccidiostat ionophore previously identified in a breast cancer screen, has anti-leukemic efficacy.

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Pathogenic mitochondrial tRNA (mt-tRNA) gene mutations represent a prominent cause of primary mitochondrial DNA (mtDNA)-related disease despite accounting for only 5%-10% of the mitochondrial genome.(1,2) Although some common mt-tRNA mutations, such as the m.3243A>G mutation, exist, the majority are rare and have been reported in only a small number of cases.

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Mutations in the four-and-a-half LIM domain 1 (FHL1) gene, which encodes a 280-amino-acid protein containing four LIM domains and a single zinc-finger domain in the N-terminal region, have been associated with a broad clinical spectrum of X-linked muscle diseases encompassing a variety of different phenotypes. Patients might present with a scapuloperoneal myopathy, a myopathy with postural muscle atrophy and generalized hypertrophy, an Emery-Dreifuss muscular dystrophy, or an early onset myopathy with reducing bodies. It has been proposed that the phenotypic variability is related to the position of the mutation within the FHL1 gene.

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