Publications by authors named "Garnham A"

Article Synopsis
  • - The study examined how the Na,K-ATPase inhibitor digoxin affects muscle content, potassium levels, and fatigue during intense exercise in healthy adults, using a double-blind crossover design with a placebo.
  • - Results showed that while muscle Na,K-ATPase binding increased with digoxin treatment, muscle isoform levels did not change, suggesting a potential adaptation mechanism to maintain Na,K-ATPase function despite the drug's effects.
  • - Exercise produced significant shifts in potassium levels, with digoxin leading to earlier fatigue and altered potassium responses compared to the placebo, highlighting digoxin's impact on muscle performance during high-intensity activities.
View Article and Find Full Text PDF

We present the first published account of a pseudoaneurysm of the Marginal artery of Drummond (MAoD) following an emergency open surgical repair of an inflammatory abdominal aortic aneurysm, in which the inferior mesenteric artery was ligated. This was hypothesized to be an iatrogenic injury secondary to retraction of the colonic mesentery during dissection of the aneurysm neck. The risk of pseudoaneurysm growth and rupture versus bowel ischaemia were evaluated in the post-operative phase.

View Article and Find Full Text PDF

Heterozygous mutations in the histone lysine acetyltransferase gene () underlie neurodevelopmental disorders, but the mechanistic roles of KAT6B remain poorly understood. Here, we show that loss of KAT6B in embryonic neural stem and progenitor cells (NSPCs) impaired cell proliferation, neuronal differentiation, and neurite outgrowth. Mechanistically, loss of KAT6B resulted in reduced acetylation at histone H3 lysine 9 and reduced expression of key nervous system development genes in NSPCs and the developing cortex, including the SOX gene family, in particular , which is a key driver of neural progenitor proliferation, multipotency and brain development.

View Article and Find Full Text PDF

Objectives: Post-operative pain control in thoracic outlet decompression (TOD) is difficult due to the complex innervation of the anatomical region. Poor post-operative pain control has been associated with worse patient experiences and prolonged inpatient stays. This study aims to identify evidence-based peri-operative analgesic strategies for thoracic outlet decompression.

View Article and Find Full Text PDF

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability and endocrine disorder caused by pathogenic variants of plant homeodomain finger gene 6 (PHF6). An understanding of the role of PHF6 in vivo in the development of the mammalian nervous system is required to advance our knowledge of how PHF6 mutations cause BFLS. Here, we show that PHF6 protein levels are greatly reduced in cells derived from a subset of patients with BFLS.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigated the relationship between testosterone levels, muscle mass, and strength in pre-menopausal females undergoing a 12-week resistance training program, finding no link with total circulating testosterone.
  • Bioavailable testosterone and the localization of androgen receptors (AR) in the nucleus were positively associated with muscle mass and strength, suggesting a unique role of these factors in muscle development for females.
  • In vitro experiments indicated that high doses of testosterone increased muscle cell size without activating the previously assumed Akt/mTOR pathway, instead enhancing the nuclear presence of the AR.
View Article and Find Full Text PDF

In muscle, digoxin inhibits Na,K-ATPase (NKA) whereas acute exercise can increase NKA gene expression, consistent with training-induced increased NKA content. We investigated whether oral digoxin increased NKA isoform mRNA expression (qPCR) in muscle at rest, during and post-exercise in 10 healthy adults, who received digoxin (DIG, 0.25 mg per day) or placebo (CON) for 14 days, in a randomised, double-blind and cross-over design.

View Article and Find Full Text PDF

It has been proposed that adult hematopoiesis is sustained by multipotent progenitors (MPPs) specified during embryogenesis. Adult-like hematopoietic stem cell (HSC) and MPP immunophenotypes are present in the fetus, but knowledge of their functional capacity is incomplete. We found that fetal MPP populations were functionally similar to adult cells, albeit with some differences in lymphoid output.

View Article and Find Full Text PDF

Both sleep loss and exercise regulate gene expression in skeletal muscle, yet little is known about how the interaction of these stressors affects the transcriptome. The aim of this study was to investigate the effect of nine nights of sleep restriction (SR), with repeated resistance exercise (REx) sessions, on the skeletal muscle transcriptome of young, trained females. Ten healthy females aged 18-35 yr old undertook a randomized cross-over study of nine nights of SR (5 h time in bed) and normal sleep (NS; ≥7 h time in bed) with a minimum 6-wk washout.

View Article and Find Full Text PDF

Understanding tissue biology's heterogeneity is crucial for advancing precision medicine. Despite the centrality of the immune system in tissue homeostasis, a detailed and comprehensive map of immune cell distribution and interactions across human tissues and demographics remains elusive. To fill this gap, we harmonised data from 12,981 single-cell RNA sequencing samples and curated 29 million cells from 45 anatomical sites to create a comprehensive compositional and transcriptional healthy map of the healthy immune system.

View Article and Find Full Text PDF

H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes in differentiation and development. Here, we investigate the molecular consequences of heterochromatin loss in cells deficient in both SUV39H1 and SUV39H2 (Suv39DKO), the major mammalian histone methyltransferase enzymes that catalyze heterochromatic H3K9me3 deposition. We reveal a paradoxical repression of protein-coding genes in Suv39DKO cells, with these differentially expressed genes principally in euchromatic (Tn5-accessible, H3K4me3- and H3K27ac-marked) rather than heterochromatic (H3K9me3-marked) or polycomb (H3K27me3-marked) regions.

View Article and Find Full Text PDF

Profunda femoris artery aneurysms are a rare form of peripheral arterial aneurysm. In this report, we present the case of an 83-year-old lady who was found to have a 65 mm aneurysm arising from the proximal left profunda femoris artery and associated pseudoaneurysm. Successful treatment was achieved using an endovascular approach in which two stents were deployed.

View Article and Find Full Text PDF

Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease.

View Article and Find Full Text PDF

The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing hematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the hematopoietic system. We found that KAT6B sustained the fetal hematopoietic stem cell pool but did not affect viability or differentiation.

View Article and Find Full Text PDF
Article Synopsis
  • ING4 and ING5 are proteins that help regulate gene expression and are part of histone acetyltransferase complexes involved in heart development.
  • Mutations in genes like KAT6A and KAT6B are linked to heart defects, and studies on mice with disrupted ING4 and ING5 reveal serious developmental issues, including heart defects.
  • The absence of these proteins leads to problems with cell development, structure, and gene expression during early embryonic stages, suggesting mutations in ING5 may contribute to human heart conditions like ventricular septal defects.*
View Article and Find Full Text PDF

Introduction: Herpesvirus infections have been highlighted as emerging diseases affecting wildlife health and the conservation of several taxa. Malignant catarrhal fever (MCF) and infectious keratoconjunctivitis (IKC) are two viruses that infect wild ruminants. Nevertheless, epidemiological data on herpesviruses in South American wild ruminants are limited.

View Article and Find Full Text PDF
Article Synopsis
  • - Alzheimer's disease (AD) is a chronic neurodegenerative disorder that leads to memory loss and the decline of essential brain functions, and while there are no definitive cures, recent medications like aducanumab and lecanemab have been approved for treatment.
  • - Despite these approvals, concerns about the effectiveness and safety of these drugs linger, with reports of adverse effects and pending validations from healthcare organizations echoing the uncertainty in the medical community.
  • - The review highlights the potential of modern nanotechnology in developing innovative diagnostic tools and treatments for AD, emphasizing the need for further research in clinical neuroscience to fully understand and address the challenges of this disease.
View Article and Find Full Text PDF
Article Synopsis
  • Recent research highlights a diverse range of infectious agents in wildlife, particularly in Chilean pudus, which may pose risks to human and animal health.
  • The study found that various pathogens were present in blood samples from wild and captive pudus, with specific percentages indicating their occurrence in the population.
  • This investigation marks the first identification of certain pathogens in wild ungulates in South America, indicating a need for further study on the potential role of pudus as infection reservoirs and transmission sources.
View Article and Find Full Text PDF

This research aimed to determine the effects of Gynostemma pentaphyllum () on exercise performance, AMP-activated protein kinase (AMPK), and mitochondrial signaling in human muscle. This randomized double-blind placebo control crossover study provided placebo or 450 mg of dried leaf extract equivalent to 2.25 g of dry leaf per day for four weeks to 16 healthy untrained young males, separated by four weeks wash-out.

View Article and Find Full Text PDF
Article Synopsis
  • Mutations in the TP53 tumor suppressor gene are linked to cancer and poor responses to chemotherapy, often thought to be due to loss-of-function, dominant-negative effects, or gain-of-function activities.
  • A study using CRISPR/Cas9 showed that eliminating various TP53 mutants did not change the growth or response to treatment of several cancer cell lines and organoids, suggesting that the gain-of-function effects may not be significant.
  • The findings indicate that loss-of-function effects of TP53 are critical for tumor growth, while targeting mutant TP53 for its gain-of-function activities may not be an effective cancer treatment strategy.
View Article and Find Full Text PDF
Article Synopsis
  • - Paternal pre-conceptual experiences, like stress or immune activation from infections, can affect the brain and behavior of offspring via changes in sperm that lead to epigenetic modifications.
  • - Using a mouse model, researchers injected male mice with a viral mimic, which resulted in their offspring showing signs of depression and altered stress responses, alongside significant changes in brain gene expression.
  • - Effects were also seen in the grand-offspring, with behavioral changes indicating an inherited impact, as well as notable alterations in the sperm microRNA profiles of both treated fathers and their male offspring.
View Article and Find Full Text PDF

Introduction: There is a dearth of evidence to document treatment of FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) in real-world settings before the introduction of FLT3 inhibitors. A retrospective cohort study was conducted to understand treatment practices prior to the availability of FLT3 inhibitors in patients with FLT3-mutated AML from two registries in France.

Methods: Patient data from January 1, 2009 to December 31, 2017 were collected from the Hauts-de-France and Midi-Pyrénées registries.

View Article and Find Full Text PDF

This article investigates the use of performance-related feedback as a strategy for overcoming spontaneous occupational stereotyping when certain social role nouns and professional terms are read. Across two studies participants were presented with two terms: a role noun (e.g.

View Article and Find Full Text PDF

Background: Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems.

View Article and Find Full Text PDF

Missense mutations in PLCG2 can cause autoinflammation with phospholipase C gamma 2-associated antibody deficiency and immune dysregulation (APLAID). Here, we generated a mouse model carrying an APLAID mutation (p.Ser707Tyr) and found that inflammatory infiltrates in the skin and lungs were only partially ameliorated by removing inflammasome function via the deletion of caspase-1.

View Article and Find Full Text PDF