1,721,009 research outputs found
Single-cell/nucleus transcriptomic and muscle pathologies
No full textRecent years have seen a dramatic improvement in RNA and DNA sequencing technologies allowing the analysis of gene expression and chromatin conformation at the single-cell or nuclei level. This permitted to evidence that cells of the human brain may have different genomes, the different cell types living in a tumor or during its development, and many other biological features, promising significant future biomedical and clinical impacts. In this chapter, we will develop the concept of single-cell or nucleus RNA sequencing discussing methods and applications in the field of muscle pathologies. We will focus on all the three types of muscles: skeletal muscle is particularly important to sustain the body and regulate the metabolism, cardiac muscle is fundamental for blood movement within vessels and oxygen and nutrient distribution, and smooth muscle is involved in the maintenance of blood pressure and in the movement of the bolus within the intestine
Genes and response to aerobic training
No full textProlonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fiber-type transformation, and substrate metabolism. Endurance adaptation results in increased muscle glycogen stores and glycogen sparing at submaximal lactate kinetics and morphological alterations, including greater type I fiber proportions per muscle area, and increased capillary and mitochondrial density. Repeated bouts of endurance exercise result in altered expression of a multiplicity of gene products, resulting in an altered muscle phenotype with improved resistance to fatigue. The effects from aerobic exercise differ greatly among individuals, depending on lifestyle factors and genetic backgrounds. The heritability estimate of the VO2max response to training was reported to be 47%. In this chapter, we consider molecular mechanisms involved in skeletal muscle changes after endurance exercises, starting from DNA polymorphisms, evaluating epigenetic transformations, discussing the regulation of key genes regulating oxidative metabolism, and integrating them in gene networks involved in the regulation of aerobic muscle performances. We also consider the involvement of noncoding RNAs in the response to the aerobic training. At the end of the chapter, we also considered beneficial effects of aerobic exercise on human health
Testo e contesto: il plico sigillato
No full textIl saggio evidenzia l'importanza delle "carte private" di Antonio Fogazzaro, di recente acquisizione, per meglio comprendere e interpretare l'officina dello scrittore vicentino, nell'anno in cui si celebra il primo centenario della morte
Salotti letterari e cenacoli filantropici femminili: il carisma di Fogazzaro
No full textIl saggio ricostruisce un capitolo importante del successo e della fortuna dello scrittore Antonio Fogazzaro illustrando, con documenti inediti, la sua presenza nei salotti letterari dell'epoca e il suo supporto ai cenacoli filantropici femminili milanesi
Tissues & organs: Biochemistry of development: Striated muscle
No full textStriated muscles are the skeletal and cardiac muscles that have distinct bands when viewed by a microscope. Although skeletal and cardiac muscles appear similar, they originate from different progenitor cells and use different evolutionarily conserved networks of transcription factors and non-coding RNAs to regulate the programs controlling cell differentiation and morphogenesis during development. Elucidating the genetic networks that govern striated muscle development not only yields insights into general principles of organogenesis, but also facilitates therapies for skeletal and cardiac muscle diseases
Correction of muscular dystrophies by CRISPR gene editing
Full text linkMuscular dystrophies are debilitating disorders that result in progressive weakness and degeneration of skeletal muscle. Although the genetic mutations and clinical abnormalities of a variety of neuromuscular diseases are well known, no curative therapies have been developed to date. The advent of genome editing technology provides new opportunities to correct the underlying mutations responsible for many monogenic neuromuscular diseases. For example, Duchenne muscular dystrophy, which is caused by mutations in the dystrophin gene, has been successfully corrected in mice, dogs, and human cells through CRISPR/Cas9 editing. In this Review, we focus on the potential for, and challenges of, correcting muscular dystrophies by editing disease-causing mutations at the genomic level. Ideally, because muscle tissues are extremely long-lived, CRISPR technology could offer a one-time treatment for muscular dystrophies by correcting the culprit genomic mutations and enabling normal expression of the repaired gene
CRISPR-Editing Therapy for Duchenne Muscular Dystrophy
No full textDuchenne muscular dystrophy (DMD) is a debilitating genetic disorder that results in progressive muscle degeneration and premature death. DMD is caused by mutations in the gene encoding dystrophin protein, a membrane-associated protein required for maintenance of muscle structure and function. Although the genetic mutations causing the disease are well known, no curative therapies have been developed to date. The advent of genome-editing technologies provides new opportunities to correct the underlying mutations responsible for DMD. These mutations have been successfully corrected in human cells, mice, and large animal models through different strategies based on CRISPR-Cas9 gene editing. Ideally, CRISPR-editing could offer a one-time treatment for DMD by correcting the genetic mutations and enabling normal expression of the repaired gene. However, numerous challenges remain to be addressed, including optimization of gene editing, delivery of gene-editing components to all the muscles of the body, and the suppression of possible immune responses to the CRISPR-editing therapy. This review provides an overview of the recent advances toward CRISPR-editing therapy for DMD and discusses the opportunities and the remaining challenges in the path to clinical translation
Single-cell transcriptomics and proteomics of skeletal muscle: Technology and applications
No full textSkeletal muscle is a heterogeneous organ, composed of different tissues. The properties of skeletal muscle are regulated by myofibers, the contracting cells. Muscles are composed of different types of myofibers that change their phenotypes in response to different stimuli. This makes possible the typical plasticity of skeletal muscle. Each myofiber can be classified according to the expression of myosin heavy-chain isoforms. In mouse muscles, there are four canonical types of myofibers (1, 2A, 2X, and 2B), with the possibility of hybrid composition (1/2A, 2A/2X, 2X/2B). In human type 2B, myofibers do not exist. Interestingly, each myofiber type has specific contractile, metabolic, and resistance to fatigue properties. This chapter will discuss methodological advances to analyze and discover specificities in terms of gene and protein expression of different myofiber types. The advantages of studying single myofibers instead of analyzing whole muscle will also be discussed. Moreover, applications of single-myofiber analysis in healthy and pathological conditions of skeletal muscle will be considered. To conclude the chapter, more recent results on noncoding RNAs of different myofiber types will be presented, evidencing the importance of this new class of genes
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