Publications by authors named "Steel K"

Athletes in Martial Arts must anticipate the target of their opponent's kick or strike to avoid contact. Findings suggest that features, e.g.

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Variants in the gene cause Norrie disease, a severe dual-sensory disorder characterized by congenital blindness due to disrupted retinal vascular development and progressive hearing loss accompanied by sensory hair cell death. encodes the secreted signaling molecule norrin. The role of norrin in the cochlea is incompletely understood.

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  • Progressive hearing loss often has a genetic basis, with specific mutations like those in the microRNA miR-96 linked to hearing impairments in both humans and mice.
  • This study examines two mouse models with different human mutations in miR-96, utilizing auditory tests and microscopy to analyze impacts on hearing and hair cell structure.
  • Results show that while both mutations cause deafness in homozygous mice, heterozygous effects vary significantly, revealing potential therapeutic targets that could delay hearing loss progression in affected mice.
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  • - Patients aged 65 and older have a higher risk of cardiovascular (CV) events, and this study aimed to evaluate the effectiveness of stress cardiac magnetic resonance (CMR) for predicting these events in this age group across multiple centers in the U.S.
  • - The research involved 1,780 seniors, finding that those with inducible ischemia or late gadolinium enhancement (LGE) showed significantly higher rates of serious CV events over nearly 5 years, while those without these conditions had a low event rate.
  • - The study concluded that both inducible ischemia and LGE are strong predictors of primary and secondary CV outcomes, indicating that CMR can be a valuable tool for risk assessment in older patients.
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Rheumatoid arthritis (RA) is an immune-mediated, chronic inflammatory condition. With modern therapeutics and evidence-based management strategies, achieving sustained remission is increasingly common. To prevent complications associated with prolonged use of immunosuppressants, drug tapering or withdrawal is recommended.

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  • - The International Knockout Mouse Consortium used a specific type of mouse mutant (knockout-first alleles) to study gene function, which should typically disrupt gene splicing and prevent normal protein production.
  • - Despite this design, the En2 splice acceptor sequence can sometimes be transcribed, allowing for the potential production of mutated proteins, leading to unexpected gene function outcomes.
  • - An analysis found that while most mutant mice didn't show significant phenotype changes due to this En2 insertion, it was present in 24 out of 35 tested mutant alleles, suggesting the need for careful monitoring of potential transcription issues in future studies.
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  • Globally, while people are living longer, many experience a decline in health due to age-related diseases, highlighting the need for better classification systems to address these issues.
  • A consensus meeting with 150 experts established criteria for identifying ageing-related pathologies, requiring a 70% agreement for approval among participants.
  • The agreed criteria focus on conditions that progress with age, contribute to functional decline, and are backed by human studies, setting a foundation for future classification and staging efforts.
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  • The study investigates the roles of two genes, Ocm and Slc26a5, in hearing loss in mice, focusing on their expression in outer hair cells and their potential interaction.
  • Mutations in both genes led to the absence of their respective mRNA and resulted in unique patterns of hearing dysfunction, indicating they don't regulate each other's expression.
  • Ocm mutants initially had normal hearing that deteriorated over time, while Slc26a5 mutants showed consistently elevated hearing thresholds, suggesting different mechanisms of auditory impairment related to outer hair cells.
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Introduction: Attaining movement proficiency under various constraints is well-researched; of particular interest here is how conscious processing and self-consciousness influence learning and performance. Current research relevant to these variables e.g.

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  • The Sgms1 gene encodes an enzyme crucial for the sphingosine-1-phosphate signaling pathway and was linked to hearing loss in mice; however, a new allele showed normal hearing initially despite mutations.
  • This mutation resulted in a reduction of Sgms1 transcript levels to 20% of normal, which was still sufficient for normal hearing at first, but led to gradual hearing loss by six months.
  • Research also indicated that abnormal structures in the inner ear and reduced electrical potential contributed to the hearing issues, and findings in a human cohort suggested that variants of the SGMS1 gene might influence hearing abilities in people.
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Background: Early invasive revascularization guided by moderate to severe ischemia did not improve outcomes over medical therapy alone, underlying the need to identify high-risk patients for a more effective invasive referral. CMR could determine the myocardial extent and matching locations of ischemia and infarction.

Objectives: This study sought to investigate if CMR peri-infarct ischemia is associated with adverse events incremental to known risk markers.

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Mutations in () cause autosomal dominant deafness-50 (DFNA50), a form of delayed-onset hearing loss. Genome editing has shown efficacy in hearing recovery through intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications, which has not been done. Here, we developed a genome editing therapy for the mutation 14C>A by screening different CRISPR systems and optimizing Cas9 expression and the sgRNA scaffold for efficient and specific mutation editing.

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This study explored video-based decision-making and eye-movement behavior as a complementary method to assess the decision-making skills and knowledge of elite junior Australian Rules (AR) Football players. Performance was measured twice over an 18-month period. This approach tested a practical and reliable assessment of decision-making and game knowledge that does not contribute to physical training load.

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Rationale: Poor asthma control in pregnancy is associated with adverse perinatal outcomes. Treatable traits improve patient outcomes but the pattern and prevalence of treatable traits in pregnant women with asthma is unknown. Whether treatable traits in pregnant women with asthma can be identified a virtual care consult is also unknown.

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Objective: Undifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or remain as seronegative undifferentiated inflammatory arthritis (UIA). Little is known about immune pathways active in the early stages of SpA and seronegative UIA, in contrast to detailed knowledge of seropositive RA. The aim of this study was to examine if specific immune pathways were active in synovial CD4+ and CD8+ T cells in EIA.

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Adult-onset progressive hearing loss is a common, complex disease with a strong genetic component. Although to date over 150 genes have been identified as contributing to human hearing loss, many more remain to be discovered, as does most of the underlying genetic diversity. Many different variants have been found to underlie adult-onset hearing loss, but they tend to be rare variants with a high impact upon the gene product.

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Mutations in ( ) cause dominant delayed onset hearing loss DFNA50 without treatment. Genome editing has shown efficacy in hearing recovery by intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications. Here, we developed an editing therapy for a C>A point mutation in the seed region of the gene, associated with hearing loss by screening gRNAs for genome editors and optimizing Cas9 and sgRNA scaffold for efficient and specific mutation editing in vitro.

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  • Deafness impacts 5% of the global population, and current treatments for genetic hearing loss are largely lacking, particularly for disorders like Norrie disease, which is caused by mutations in the NDP gene and leads to dual sensory deprivation.
  • Researchers utilized a Norrie disease mouse model to test a gene therapy approach, delivering the human NDP cDNA through an adeno-associated viral vector (AAV)9 at various developmental stages.
  • Neonatal treatment showed promising results, preventing cochlear hair cell death and restoring both auditory function and retinal health, indicating potential for effective clinical therapy for Norrie disease-related hearing loss.
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  • Hearing loss can result from an inability to maintain the proper ionic environment in sensory hair cells, leading to a lower endocochlear potential.
  • Researchers used a genetic strategy in a mouse model to investigate if they could reverse this type of hearing loss by activating gene transcription at different ages.
  • Their findings suggest that early intervention can restore normal auditory responses and protect hair cells from further damage, indicating a critical window for effective treatment that could potentially apply to other conditions as well.
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CD8 T cells drive anti-cancer immunity in response to antigen-presenting cells such as dendritic cells and subpopulations of monocytes and macrophages. While CD14 classical monocytes modulate CD8 T cell responses, the contributions of CD16 nonclassical monocytes to this process remain unclear. Herein we explored the role of nonclassical monocytes in CD8 T cell activation by utilizing E2-deficient (E2) mice that lack nonclassical monocytes.

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IL-17A+ CD8+ T-cells, termed Tc17 cells, have been identified at sites of inflammation in several immune-mediated inflammatory diseases. However, the biological function of human IL-17A+ CD8+ T-cells is not well characterized, likely due in part to the relative scarcity of these cells. Here, we expanded IL-17A+ CD8+ T-cells from healthy donor PBMC or bulk CD8+ T-cell populations using an in vitro polarization protocol.

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Bacteria produce a variety of polysaccharides with functional roles in cell surface coating, surface and host interactions, and biofilms. We have identified an 'Orphan' bacterial cellulose synthase catalytic subunit (BcsA)-like protein found in four model pseudomonads, P. aeruginosa PA01, P.

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CD69+CD103+ tissue-resident memory T (T) cells are important drivers of inflammation. To decipher their role in inflammatory arthritis, we apply single-cell, high-dimensional profiling to T cells from the joints of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identify three groups of synovial CD8+CD69+CD103+ T cells: cytotoxic and regulatory T (Treg)-like T cells are present in both PsA and RA, while CD161+CCR6+ type 17-like T cells with a pro-inflammatory cytokine profile (IL-17A+TNFα+IFNγ+) are specifically enriched in PsA.

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  • - Non-syndromic sensorineural hearing loss (SNHL) is a common sensory disorder with complex genetics; a new mutation in the CCDC50 gene linked to SNHL was found in a Spanish family.
  • - Mouse models showed normal hearing up to six months, suggesting that reduced protein levels (haploinsufficiency) aren’t the cause of hearing loss in this case.
  • - Laboratory studies revealed that specific mutations in CCDC50 lead to abnormal protein aggregates, indicating that these mutations affect protein function in a dominant-negative manner rather than simply reducing protein levels.
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