Protein turnover defines the balance between two continuous and complex processes of protein metabolism, synthesis and degradation, which determine their deposition in tissues. Although the liver and intestine have been studied extensively for their important roles in protein digestion, absorption and metabolism, the study of protein metabolism has focused mainly on skeletal muscle tissue to understand the basis for its growth. Due to the high adaptability of skeletal muscle, its protein turnover is greatly affected by different internal and external factors, contributing to carcass lean-yield and animal growth. Amino acid (AA) labelling and tracking using isotope tracer methodology, together with the study of myofiber type profiling, signal transduction pathways and gene expression, has allowed the analysis of these mechanisms from different perspectives. Positive stimuli such as increased nutrient availability in the diet (e.g., AA), physical activity, the presence of certain hormones (e.g., testosterone) or a more oxidative myofiber profile in certain muscles or pig genotypes promote increased upregulation of translation and transcription-related genes, activation of mTORC1 signalling mechanisms and increased abundance of satellite cells, allowing for more efficient protein synthesis. However, fasting, animal aging, inactivity and stress, inflammation or sepsis produce the opposite effect. Deepening the understanding of modifying factors and their possible interaction may contribute to the design of optimal strategies to better control tissue growth and nutrient use (i.e., protein and AA), and thus advance the precision feeding strategy.

Insects have been consumed as food in diverse cultures worldwide, gaining recognition as a sustainable and nutritious food source. This systematic review aims to update information on the impact of insect consumption on human health based on human randomized controlled trials (RCTs) and allergenicity assessment studies. Following PRISMA guidelines, studies published in the last 10 years were analyzed. From one-thousand and sixty-three retrieved references, nine RCTs and five allergenicity studies were analyzed. Post-prandial amino acid levels increased after insect protein consumption. In comparison with other protein sources, insect protein showed no significant differences in the area under the curve (AUC) values for essential amino acids but tended to have lower peaks and peak later. In terms of muscle protein synthesis, there were no significant differences between insect protein and other protein sources. Glucose levels did not differ; however, insulin levels were lower after the consumption of insect-based products. The effects on inflammatory markers and microbiota composition were inconclusive and the studies did not show significant effects on appetite regulation. Allergenicity assessments revealed a sensitisation and cross-reactivity between insect allergens and known allergens. A partial reduction of cross-allergenicity was observed via thermal processing. Insect protein is an adequate protein source with promising health benefits; however, further research is needed to fully understand its potential and optimise its inclusion into the human diet.

A model explaining the dietary-protein-driven post-natal skeletal muscle growth and protein turnover in the rat is updated, and the mechanisms involved are described, in this narrative review. Dietary protein controls both bone length and muscle growth, which are interrelated through mechanotransduction mechanisms with muscle growth induced both from stretching subsequent to bone length growth and from internal work against gravity. This induces satellite cell activation, myogenesis and remodelling of the extracellular matrix, establishing a growth capacity for myofibre length and cross-sectional area. Protein deposition within this capacity is enabled by adequate dietary protein and other key nutrients. After briefly reviewing the experimental animal origins of the growth model, key concepts and processes important for growth are reviewed. These include the growth in number and size of the myonuclear domain, satellite cell activity during post-natal development and the autocrine/paracrine action of IGF-1. Regulatory and signalling pathways reviewed include developmental mechanotransduction, signalling through the insulin/IGF-1-PI3K-Akt and the Ras-MAPK pathways in the myofibre and during mechanotransduction of satellite cells. Likely pathways activated by maximal-intensity muscle contractions are highlighted and the regulation of the capacity for protein synthesis in terms of ribosome assembly and the translational regulation of 5-TOPmRNA classes by mTORC1 and LARP1 are discussed. Evidence for and potential mechanisms by which volume limitation of muscle growth can occur which would limit protein deposition within the myofibre are reviewed. An understanding of how muscle growth is achieved allows better nutritional management of its growth in health and disease.

Despite advances in the nutritional support of low birth weight and early-weaned piglets, most experience reduced extrauterine growth performance. To further optimize nutritional support and develop targeted intervention strategies, the mechanisms that regulate the anabolic response to nutrition must be fully understood. Knowledge gained in these studies represents a valuable intersection of agriculture and biomedical research, as low birth weight and early-weaned piglets face many of the same morbidities as preterm and low birth weight infants, including extrauterine growth faltering and reduced lean growth. While the reasons for poor growth performance are multifaceted, recent studies have increased our understanding of the role of nutrition in the regulation of skeletal muscle growth in the piglet. The purpose of this review is to summarize the published literature surrounding advances in the current understanding of the anabolic signaling that occurs after a meal and how this response is developmentally regulated in the neonatal pig. It will focus on the regulation of protein synthesis, and especially the upstream and downstream effectors surrounding the master protein kinase, mechanistic target of rapamycin complex 1 (mTORC1) that controls translation initiation. It also will examine the regulatory pathways associated with the postprandial anabolic agents, insulin and specific amino acids, that are upstream of mTORC1 and lead to its activation. Lastly, the integration of upstream signaling cascades by mTORC1 leading to the activation of translation initiation factors that regulate protein synthesis will be discussed. This review concludes that anabolic signaling cascades are stimulated by both insulin and amino acids, especially leucine, through separate pathways upstream of mTORC1, and that these stimulatory pathways result in mTORC1 activation and subsequent activation of downstream effectors that regulate translation initiation Additionally, it is concluded that this anabolic response is unique to the skeletal muscle of the neonate, resulting from increased sensitivity to the rise in both insulin and amino acid after a meal. However, this response is dampened in skeletal muscle of the low birth weight pig, indicative of anabolic resistance. Elucidation of the pathways and regulatory mechanisms surrounding protein synthesis and lean growth allow for the development of potential targeted therapeutics and intervention strategies both in livestock production and neonatal care.

Alzheimer\'s disease (AD) is characterized by complex etiology, long-lasting pathogenesis, and cell-type-specific alterations. Currently, there is no cure for AD, emphasizing the urgent need for a comprehensive understanding of cell-specific pathology. Astrocytes, principal homeostatic cells of the central nervous system, are key players in the pathogenesis of neurodegenerative diseases, including AD. Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways. Tumor-derived and immortalized astrocytic cell lines, alongside the emerging technology of adult induced pluripotent stem cells, are widely used to study cellular dysfunction in AD. Surprisingly, no stable cell lines were available from genetic mouse AD models. Recently, we established immortalized hippocampal astroglial cell lines from amyloid-β precursor protein/presenilin-1/Tau triple-transgenic (3xTg)-AD mice (denominated as wild type (WT)- and 3Tg-iAstro cells) using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection, thereby maintaining natural heterogeneity of primary cultures. Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling, mitochondrial dysfunctions, disproteostasis, altered homeostatic and signaling support to neurons, and blood-brain barrier models. Here we provide a comparative overview of the most used models to study astrocytes in vitro, such as primary culture, tumor-derived cell lines, immortalized astroglial cell lines, and induced pluripotent stem cell-derived astrocytes. We conclude that immortalized WT- and 3Tg-iAstro cells provide a non-competitive but complementary, low-cost, easy-to-handle, and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.

Skeletal muscle mass is determined by the balance between muscle protein synthesis (MPS) and degradation. Several intracellular signaling pathways control this balance, including mammalian/mechanistic target of rapamycin (mTOR) complex 1 (C1). Activation of this pathway in skeletal muscle is controlled, in part, by nutrition (e.g., amino acids and alcohol) and exercise (e.g., resistance exercise (RE)). Acute and chronic alcohol use can result in myopathy, and evidence points to altered mTORC1 signaling as a contributing factor. Moreover, individuals who regularly perform RE or vigorous aerobic exercise are more likely to use alcohol frequently and in larger quantities. Therefore, alcohol may antagonize beneficial exercise-induced increases in mTORC1 pathway signaling. The purpose of this review is to synthesize up-to-date evidence regarding mTORC1 pathway signaling and the independent and combined effects of acute alcohol and RE on activation of the mTORC1 pathway. Overall, acute alcohol impairs and RE activates mTORC1 pathway signaling; however, effects vary by model, sex, feeding, training status, quantity, etc., such that anabolic stimuli may partially rescue the alcohol-mediated pathway inhibition. Likewise, the impact of alcohol on RE-induced mTORC1 pathway signaling appears dependent on several factors including nutrition and sex, although many questions remain unanswered. Accordingly, we identify gaps in the literature that remain to be elucidated to fully understand the independent and combined impacts of alcohol and RE on mTORC1 pathway signaling.

Translation of RNA to protein is a key feature of cellular life. The fidelity of this process mainly depends on the availability of correctly charged tRNAs. Different domains of tRNA synthetase (aaRS) maintain translation quality by ensuring the proper attachment of particular amino acid with respective tRNA, thus it establishes the rule of genetic code. However occasional errors by aaRS generate mischarged tRNAs, which can become lethal to the cells. Accurate protein synthesis necessitates hydrolysis of mischarged tRNAs. Various cis and trans-editing proteins are identified which recognize these mischarged products and correct them by hydrolysis. Trans-editing proteins are homologs of cis-editing domains of aaRS. The trans-editing proteins work in close association with aaRS, Ef-Tu, and ribosome to prevent global mistranslation and ensures correct charging of tRNA. In this review, we discuss the major trans-editing proteins and compared them with their cis-editing counterparts. We also discuss their structural features, biochemical activity and role in maintaining cellular protein homeostasis.

Adequate protein intake is essential for the maintenance of whole-body protein mass. Different methodological approaches are used to substantiate the evidence for the current protein recommendations, and it is continuously debated whether older adults require more protein to counteract the age-dependent loss of muscle mass, sarcopenia. Thus, the purpose of this critical narrative review is to outline and discuss differences in the approaches and methodologies assessing the protein requirements and, hence, resulting in controversies in current protein recommendations for healthy older adults. Through a literature search, this narrative review first summarises the historical development of the Food and Agriculture Organization/World Health Organization/United Nations University setting of protein requirements and recommendations for healthy older adults. Hereafter, we describe the various types of studies (epidemiological studies and protein turnover kinetic measurements) and applied methodological approaches founding the basis and the different recommendations with focus on healthy older adults. Finally, we discuss important factors to be considered in future studies to obtain evidence for international agreement on protein requirements and recommendations for healthy older adults. We conclude by proposing future directions to determine \'true\' protein requirements and recommendations for healthy older adults.

Protein design is the field of synthetic biology that aims at developing de novo custom-made proteins and peptides for specific applications. Despite exploring an ambitious goal, recent computational advances in both hardware and software technologies have paved the way to high-throughput screening and detailed design of novel folds and improved functionalities. Modern advances in the field of protein design for small molecule targeting are described in this review, organized in a step-by-step fashion: from the conception of a new or upgraded active binding site, to scaffold design, sequence optimization, and experimental expression of the custom protein. In each step, contemporary examples are described, and state-of-the-art software is briefly explored.

Post-exercise recovery is a broad term that refers to the restoration of training capacity. After training or competition, there is fatigue accumulation and a reduction in sports performance. In the hours and days following training, the body recovers and performance is expected to return to normal or improve. ScienceDirect, PubMed/MEDLINE, and Google Scholar databases were reviewed to identify studies and position declarations examining the relationship between nutrition and sports recovery. As an evidence-based framework, a 4R\'s approach to optimizing post-exercise recovery was identified: (i) Rehydration-a fundamental process that will depend on the athlete, environment and sports event; (ii) Refuel-the consumption of carbohydrates is not only important to replenish the glycogen reserves but also to contribute to the energy requirements for the immune system and tissue reparation. Several bioengineered carbohydrates were discussed but further research is needed; (iii) Repair-post-exercise ingestion of high-quality protein and creatine monohydrate benefit the tissue growth and repair; and (iv) Rest-pre-sleep nutrition has a restorative effect that facilitates the recovery of the musculoskeletal, endocrine, immune, and nervous systems. Nutritional consultancy based on the 4R\'s is important for the wise stewardship of the hydration, feeding, and supplementation strategies to achieve a timely recovery.