Regulatory polymorphisms in the bovine Ankyrin 1 gene promoter are associated with tenderness and intramuscular fat content

peer-reviewedRecent QTL and gene expression studies have highlighted ankyrins as positional and functional candidate genes for meat quality. Our objective was to characterise the promoter region of the bovine ankyrin 1 gene and to test polymorphisms for association with sensory and technological meat quality measures. Results Seven novel promoter SNPs were identified in a 1.11 kb region of the ankyrin 1 promoter in Angus, Charolais and Limousin bulls (n = 15 per breed) as well as 141 crossbred beef animals for which meat quality data was available. Eighteen haplotypes were inferred with significant breed variation in haplotype frequencies. The five most frequent SNPs and the four most frequent haplotypes were subsequently tested for association with sensory and technological measures of meat quality in the crossbred population. SNP1, SNP3 and SNP4 (which were subsequently designated regulatory SNPs) and SNP5 were associated with traits that contribute to sensorial and technological measurements of tenderness and texture; Haplotype 1 and haplotype 4 were oppositely correlated with traits contributing to tenderness (P < 0.05). While no single SNP was associated with intramuscular fat (IMF), a clear association with increased IMF and juiciness was observed for haplotype 2. Conclusion The conclusion from this study is that alleles defining haplotypes 2 and 4 could usefully contribute to marker SNP panels used to select individuals with improved IMF/juiciness or tenderness in a genome-assisted selection framework.Department of Agriculture, Fisheries and Food, Ireland, through the Food Institutional Research Measur

Transcriptome analysis of porcine M. semimembranosus divergent in intramuscular fat as a consequence of dietary protein restriction

peer-reviewedBackground: Intramuscular fat (IMF) content is positively correlated with aspects of pork palatability, including flavour, juiciness and overall acceptability. The ratio of energy to protein in the finishing diet of growing pigs can impact on IMF content with consequences for pork quality. The objective of this study was to compare gene expression profiles of Musculus semimembranosus (SM) of animals divergent for IMF as a consequence of protein dietary restriction in an isocaloric diet. The animal model was derived through the imposition of low or high protein diets during the finisher stage in Duroc gilts. RNA was extracted from post mortem SM tissue, processed and hybridised to Affymetrix porcine GeneChip® arrays. Results: IMF content of SM muscle was increased on the low protein diet (3.60 ± 0.38% versus 1.92 ± 0.35%). Backfat depth was also greater in animals on the low protein diet, and average daily gain and feed conversion ratio were lower, but muscle depth, protein content and moisture content were not affected. A total of 542 annotated genes were differentially expressed (DE) between animals on low and high protein diets, with 351 down-regulated and 191 up-regulated on the low protein diet. Transcript differences were validated for a subset of DE genes by qPCR. Alterations in functions related to cell cycle, muscle growth, extracellular matrix organisation, collagen development, lipogenesis and lipolysis, were observed. Expression of adipokines including LEP, TNFα and HIF1α were increased and the hypoxic stress response was induced. Many of the identified transcriptomic responses have also been observed in genetic and fetal programming models of differential IMF accumulation, indicating they may be robust biological indicators of IMF content. Conclusion: An extensive perturbation of overall energy metabolism in muscle occurs in response to protein restriction. A low protein diet can modulate IMF content of the SM by altering gene pathways involved in lipid biosynthesis and degradation; however this nutritional challenge negatively impacts protein synthesis pathways, with potential consequences for growth.Department of Agriculture, Food and the Marine, Ireland - Food Institutional Research Measur

Circulating irisin levels in newly diagnosed obstructive sleep apnea patients

Introduction: Obstructive sleep apnea syndrome (OSAS) is commonly associated with obesity, insulin resistance, metabolic syndrome, hypertension, and coronary artery disease. Irisin is a newly identified myokine and its serum concentration was found to be correlated with cardiac troponin and creatin kinase-MB in acute myocardial infarction patients. Furthermore, irisin levels were positively associated with endothelium-dependent vasodilation in type 2 diabetic patients.Aim: In this study, we aimed to investigate serum irisin level in the newly diagnosed OSAS patients.Materials and Methods: After obtaining ethical approval, 32 OSAS patients were included. All patients gave written informed consent. Diagnosis of OSAS was verified by an overnight polysomnography (PSG) and made by an apnea hypopnea index equal to or higher than 5. Venous blood samples were collected in the morning between 08.00 – 10.00 after PSG (n=25) or after one-night CPAP treatment (n=7). Serum irisin concentrations were studied by ELISA.Results and Conclusion: Serum irisin concentrations were significantly higher in newly diagnosed OSAS group than in OSAS group after one night of CPAP treatment (199.7±42.4 vs 159.7±18.3 ng/mL respectively; p<0.01). These results suggest that increased serum irisin levels can be reduced by CPAP treatment and elevated serum irisin levels may be due to increased respiratory muscle activity and body temperature.

Dosing and safety profile of aficamten in symptomatic obstructive hypertrophic cardiomyopathy: results from from SEQUOIA‐HCM

Background: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA‐HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). Methods and Results: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5–20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site‐interpreted Valsalva left ventricular outflow tract gradient &lt;30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8–24), and washout (weeks 24–28), and included major adverse cardiac events, new‐onset atrial fibrillation, implantable cardioverter‐defibrillator discharges, LVEF &lt;50%, and treatment‐emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5‐, 10‐, 15‐, and 20‐mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by −0.9% (95% CI, −1.3 to −0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per‐protocol dose reduction for site‐interpreted LVEF &lt;50%. There were no treatment interruptions or heart failure worsening for LVEF &lt;50%. No major adverse cardiovascular events were associated with aficamten, and treatment‐emergent adverse events were similar between treatment groups, including atrial fibrillation. Conclusions: A site‐based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA‐HCM

Resistances against Hydropower Projects as Place-based Struggles: The Case of Artvin, Turkey

The dissertation examines the implications of place-based action for a rethinking of democratic politics. The research is based on the struggles against hydropower projects in Artvin, a small city in the Black Sea Region of Turkey. The dissertation traces the effects of the dams as spatial interventions in the region based on the accounts of the inhabitants, field observations, official reports, and academic articles; it maps the institutional structures that enable these spatial interventions and reveals ways citizens challenge these institutional structures. The dissertation offers a phenomenological approach as an important addition to social constructivist approaches to understanding the struggles against the run-of-the-river type hydropower projects in the region. Social constructivist approaches to place-based struggles have been significant in unpacking the power dynamics within which spatial interventions are made possible and are resisted. These approaches evaluated place-based struggles based on their handling of heterogeneity and difference, their potential in dismantling of capitalism, their ability to articulate their problems in more structural terms and their ability to be extroverted and situate themselves in broader networks. Phenomenological approaches enable us to articulate the emphasis these struggles put on the significance of “implacement” as a social and physical experience for living beings. The dissertation argues that the anti-hydropower struggles in Turkey—through their emphasis on protecting “life spaces”— underlined a form of placial ethics. “Life spaces” encompassed both human networks of relationships and their embeddedness in the entire eco-system. This placial ethics challenged the existing cost-benefit analysis and redefined the destruction of landscape as a collective loss. This ethics-based politics rendered participatory collective decision-making imperative for spatial interventions and required prioritization of politics of place over partisan politics. The politics aimed at protecting life space thus redefines the nature of interests at stake as well as the nature of democratic participation.Ph.D

Special Issue: Advances in Bioprocess Technology

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