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Of note, MC3482 increased the expression and the activity of adipose triglyceride lipase, without modulating hormone-sensitive lipase. Our findings reveal that SIRT5 inhibition stimulates brown adipogenesis in vitro, supporting this approach as a strategy to stimulate BAT and counteract obesity.DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate RT advances that are still uncharacterized. Picrotoxin In order to characterize these advanced initiation events, we monitored the whole genome RT from six independent human cell lines treated with low doses of aphidicolin. We report that RT advances are cell-type-specific and involve large heterochromatin domains. Importantly, we found that some major late to early RT advances can be inherited by the unstressed next-cellular generation, which is a unique process that correlates with enhanced chromatin accessibility, as well as modified replication origin landscape and gene expression in daughter cells. Collectively, this work highlights how low replication stress may impact cellular identity by RT advances events at a subset of chromosomal domains.Neo-Darwinism presumes that biological variation is a product of random genetic replication errors and natural selection. Cognition-Based Evolution (CBE) asserts a comprehensive alternative approach to phenotypic variation and the generation of biological novelty. In CBE, evolutionary variation is the product of natural cellular engineering that permits purposive genetic adjustments as cellular problem-solving. CBE upholds that the cornerstone of biology is the intelligent measuring cell. Since all biological information that is available to cells is ambiguous, multicellularity arises from the cellular requirement to maximize the validity of available environmental information. This is best accomplished through collective measurement purposed towards maintaining and optimizing individual cellular states of homeorhesis as dynamic flux that sustains cellular equipoise. The collective action of the multicellular measurement and assessment of information and its collaborative communication is natural cellular engineering. Its yield is linked cellular ecologies and mutualized niche constructions that comprise biofilms and holobionts. In this context, biological variation is the product of collective differential assessment of ambiguous environmental cues by networking intelligent cells. Such concerted action is enabled by non-random natural genomic editing in response to epigenetic impacts and environmental stresses. Random genetic activity can be either constrained or deployed as a 'harnessing of stochasticity'. Therefore, genes are cellular tools. Selection filters cellular solutions to environmental stresses to assure continuous cellular-organismal-environmental complementarity. Since all multicellular eukaryotes are holobionts as vast assemblages of participants of each of the three cellular domains (Prokaryota, Archaea, Eukaryota) and the virome, multicellular variation is necessarily a product of co-engineering among them.
Dietary intakes must cover protein and essential amino acid (EAA) requirements. For this purpose, different methods have been developed such as the nitrogen balance method, factorial method, or AA tracer studies. However, these methods are either invasive or imprecise, and the Food and Agriculture Organization of the United Nations (FAO, 2013) recommends new methods and, in particular, metabolomics. The aim of this study is to determine total protein/EAA requirement in the plasma and urine of growing rats.
36 weanling rats were fed with diets containing 3, 5, 8, 12, 15, and 20% protein for 3 weeks. During experimentation, urine was collected using metabolic cages, and blood from the portal vein and vena was taken at the end of the experiment. Metabolomics analyses were performed using LC-MS, and the data were analyzed with a multivariate analysis model, partial least Squares (PLS) regression, and independent component-discriminant analysis (ICDA). Each discriminant metabolite identified by PLS or ICDA was tested by one-way ANOVA to evaluate the effect of diet.
PLS and ICDA allowed us to identify discriminating metabolites between different diet groups. Protein deficiency led to an increase in the AA catabolism enzyme systems inducing the production of breakdown metabolites in the plasma and urine.
These results indicate that metabolites are specific for the state of EAA deficiency and sufficiency. Some types of biomarkers such as AA degradation metabolites appear to be specific candidates for protein/EAA requirement.
These results indicate that metabolites are specific for the state of EAA deficiency and sufficiency. Some types of biomarkers such as AA degradation metabolites appear to be specific candidates for protein/EAA requirement.Athlete's heart (AH) is the result of morphological and functional cardiac modifications due to long-lasting athletic training. Athletes can develop very marked structural myocardial changes, which may simulate or cover unknown cardiomyopathies. The differential diagnosis between AH and cardiomyopathy is necessary to prevent the risk of catastrophic events, such as sudden cardiac death, but it can be a challenging task. The improvement of the imaging modalities and the introduction of the new technologies in cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) can allow overcoming this challenge. Therefore, the radiologist, specialized in cardiac imaging, could have a pivotal role in the differential diagnosis between structural adaptative changes observed in the AH and pathological anomalies of cardiomyopathies. In this review, we summarize the main CMR and CCT techniques to evaluate the cardiac morphology, function, and tissue characterization, and we analyze the imaging features of the AH and the key differences with the main cardiomyopathies.
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