CrossTalk opposing view: Ketone bodies are not an important metabolic fuel for the heart

SCOPUS: no.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Rebuttal from Manoja K. Brahma, Adam R. Wende and Kyle S. McCommis

SCOPUS: no.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Beyond flight operations: Assessing the environmental impact of aircraft maintenance through life cycle assessment

As the aviation industry strives to minimise its environmental footprint, understanding the full life cycle impacts, including maintenance, becomes essential for sustainable development. This paper addresses the critical research gap in the environmental assessment of aircraft maintenance by conducting a comprehensive life cycle assessment based on an Airbus A320 aircraft. By combining a top-down check-level analysis and a detailed examination of the aircraft manufacturer's maintenance planning document, this study provides significant insights into the environmental implications of maintenance activities. The check-level analysis provides a general overview, while the analysis of the maintenance planning document delves into individual tasks, enabling the identification of components with the highest ecological impacts. This research emphasises the importance of including aircraft maintenance activities in life cycle assessment studies and provides valuable guidance for researchers, industry practitioners, and policy makers in prioritising sustainability measures and enhancing the environmental performance of aircraft throughout their life cycle.Industrial Design EngineeringDesign for SustainabilityGroup Dransfel

Glucagon receptor signaling regulates energy metabolism via hepatic farnesoid X receptor and fibroblast growth factor 21.

Glucagon, an essential regulator of glucose and lipid metabolism, also promotes weight loss, in part through potentiation of fibroblast growth factor 21 (FGF21) secretion. However, FGF21 is only a partial mediator of metabolic actions ensuing from glucagon receptor (GCGR) activation, prompting us to search for additional pathways. Intriguingly, chronic GCGR agonism increases plasma bile acid levels. We hypothesized that GCGR agonism regulates energy metabolism, at least in part, through farnesoid X receptor (FXR). To test this hypothesis, we studied whole-body and liver-specific FXR-knockout (Fxr∆liver) mice. Chronic GCGR agonist (IUB288) administration in diet-induced obese (DIO) Gcgr, Fgf21, and Fxr whole-body or liver-specific knockout (∆liver) mice failed to reduce body weight when compared with wild-type (WT) mice. IUB288 increased energy expenditure and respiration in DIO WT mice, but not Fxr∆liver mice. GCGR agonism increased [14C]palmitate oxidation in hepatocytes isolated from WT mice in a dose-dependent manner, an effect blunted in hepatocytes from Fxr∆liver mice. Our data clearly demonstrate that control of whole-body energy expenditure by GCGR agonism requires intact FXR signaling in the liver. This heretofore-unappreciated aspect of glucagon biology has implications for the use of GCGR agonism in the therapy of metabolic disorders

High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction

Novel biomarkers are needed to better identify - and distinguish - heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4(+) T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.e., discovery/validation) each of both male and female patients with HFpEF (n = 12/10), HF with reduced EF (HFrEF; n = 7/5), and volunteers lacking clinical evidence of HF (CON; n = 7/5). RRBS is the gold-standard platform for measuring genome-wide DNA methylation changes at single-cytosine resolution in hypothesis-generating studies. We identified three hypomethylated HFpEF-specific differentially methylated positions (DMPs) associated with FOXB1, ELMOD1, and DGKH genes wherein ROC curve analysis revealed that increased expression levels had a reasonable diagnostic performance in predicting HFpEF (AUC ≥ 0.8, p  0.05). Besides, increased expression levels of SETD7-RELA-IL6 axis significantly discriminated overweight/obese HFpEF vs. HFrEF patients (AUC = 1; p = 0.001, p = 0.006, p = 0.006, respectively). We support an emerging dogma that indirect epigenetic testing via high-resolution RRBS methylomics represents a non-invasive tool that may enable easier access to both diagnostic and mechanistic insights of HFpEF. An epigenetic-oriented dysregulation of network-derived SETD7-RELA-IL6 axis in circulating CD4(+) T lymphocytes may drive pro-inflammatory responses which, in turn, may lead to cardiac remodeling in overweight/obese HFpEF

Gender-dependent effects of high-fat lard diet on cardiac function in C57Bl/6J mice.

Item does not contain fulltextIncreased availability of fatty acids released from insulin-resistant adipose tissue may lead to excess fatty acid uptake in nonadipose organs, including the heart. Accumulation of toxic fatty acid intermediates may affect cardiac function. Our aim was to identify to which extent high-fat diet feeding leads to alterations in cardiac function and whether this depends on gender and (or) duration of high-fat diet feeding. Male and female C57Bl/6J mice (n = 8 per group) of 12 to 16 weeks old were fed a low-fat (10% energy) or high-fat (45% energy) lard diet for 6 or 12 weeks. Plasma lipid levels, echocardiography, and left ventricular pressure-volume relationships were obtained at 2, 1, and 0 weeks before termination, respectively. In both male and female mice, the high-fat diet increased body weight and plasma lipid content. At 10 weeks, significant increases were observed for plasma total cholesterol (males: +44%; females: +86%), phospholipids (+16% and +34%), and triglycerides (+27% and +53%) (all p < 0.001). In male mice, but not in female mice, the high-fat diet significantly affected cardiac function at 12 weeks with increased end-systolic volume (25.4 +/- 6.2 vs. 17.0 +/- 6.7 microL, p < 0.05), increased end-systolic pressure (72.1 +/- 6.9 vs. 63.6 +/- 6.9 mm Hg, p < 0.01), and decreased ejection fraction (61.2% +/- 4.5% vs. 68.1% +/- 3.7%, p < 0.01), indicating reduced systolic function. Multiple linear regression analysis indicated a significant diet-gender interaction for end-systolic volume and ejection fraction. In conclusion, high-fat diet feeding increased body weight and plasma lipid levels in male and in female mice, but resulted in impairment of cardiac function only in males.1 april 201

Exploring failures at the team level in offshore-outsourced software development projects

Offshore-outsourced software development (OOSD) projects involvemultifaceted risks throughout the project execution, as they are handed over tothird-party organizations and thus are exposed to more risks than in domesticoutsourcing or captive offshoring. We concentrate on failed OOSD projects inthis paper and analyze the unique aspects of such projects at the team level thatlead to failures. Using the grounded theory approach, we conducted semistructuredinterviews with 19 project managers involved in OOSD projectfailures from the vendor and client sides, who are based in India or Switzerland.We developed a set of propositions regarding multiple teams in the OOSDproject context to explain failures. Integration of inter-organizational offshoreand onshore teams from the vendor and client sides was found to beindispensable in avoiding project failures. Six categories of unique aspects thatlead to OOSD project failures were identified and discussed in this exploratorywork