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Topic Review
IPSC Preparation and Epigenetic Memory
The derivation of induced pluripotent stem cells (iPSCs) from somatic human cells by Takahashi and Yamanaka in 2007 represented a turning point for the field. For the first time, they provided isogenic pluripotent cells with the potential for personalized cell replacement therapies; no ethical issues would be created by using the somatic cells. This opportunity marks a decisive step compared to the generation of human embryonic stem cells (ESCs) arranged by Thomson et al. in 1998. The production of induced pluripotent stem cells (iPSCs) represent a breakthrough in regenerative medicine, providing new opportunities for understanding basic molecular mechanisms of human development and molecular aspects of degenerative diseases.
  • 709
  • 22 Jun 2021
Topic Review
Small Ras GTPases in Fungi
Monomeric GTPases, which belong to the Ras superfamily, are small proteins involved in many biological processes. The most studied families are Ras, Rho, Rab, Ran, Arf, and Miro, and recently, a new family named Big Ras GTPases was reported. As a general rule, the proteins of all families have five characteristic motifs (G1–G5), and some specific features for each family have been described. The main functions described for monomeric GTPases in fungi include morphogenesis, secondary metabolism, vesicle trafficking, and virulence.
  • 710
  • 21 Jun 2021
Topic Review
Minor Intron Splicing
Pre-mRNA splicing is an essential step in gene expression and is catalyzed by two machineries in eukaryotes: the major (U2 type) and minor (U12 type) spliceosomes. While the majority of introns in humans are U2 type, less than 0.4% are U12 type, also known as minor introns (mi-INTs), and require a specialized spliceosome composed of U11, U12, U4atac, U5, and U6atac snRNPs. The high evolutionary conservation and apparent splicing inefficiency of U12 introns have set them apart from their major counterparts and led to speculations on the purpose for their existence.
  • 916
  • 21 Jun 2021
Topic Review
Arteriovenous and Cavernous Malformations
Brain arteriovenous malformations (BAVMs) are predominantly congenital vascular disorders that may arise anywhere inside of the central nervous system. They are comprised of one or more arterial feeders supplying a vascular nidus, and one or more draining veins. The nidus itself represents the site where arterial blood is shunted directly into the venous system without an interpolating network of capillaries.
  • 578
  • 18 Jun 2021
Topic Review
Pericytes
Pericytes are increasingly recognized as being important in the control of blood–brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse–human species differences have contributed to confusion.
  • 538
  • 17 Jun 2021
Topic Review
MicroRNAs in Regulation of Melanogenesis
Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered melanogenesis is observed in several pigmentation disorders. Melanogenesis occurs in specialized cells called melanocytes, physically and functionally related by means of autocrine and paracrine interplay to other skin cell types. Several external and internal factors control melanin biosynthesis and operate through different intracellular signaling pathways, which finally leads to the regulation of microphthalmia-associated transcription factor (MITF), the key transcription factor involved in melanogenesis and the expression of the main melanogenic enzymes, including TYR, TYRP-1, and TYRP-2. Epigenetic factors, including microRNAs (miRNAs), are involved in melanogenesis regulation. miRNAs are small, single-stranded, non-coding RNAs, of approximately 22 nucleotides in length, which control cell behavior by regulating gene expression, mainly by binding the 3′ untranslated region (3′-UTR) of target mRNAs.
  • 802
  • 17 Jun 2021
Topic Review
DNA Homeostasis and Senescence
As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations.  
  • 641
  • 17 Jun 2021
Topic Review
Mesenchymal Stromal Cell Aging
Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status.
  • 601
  • 16 Jun 2021
Topic Review
Redox Homeostasis in Muscular Dystrophies
Reactive oxygen species are (ROS) are signaling molecules moderately and continuously produced by skeletal muscles as a consequence of their contractile activity and high mitochondrial oxygen consumption. The main source of ROS production is located in the cytosol through the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX enzymes), xanthine oxidase (XO), and nitric oxide synthase (NOS), and by the mitochondrial electron transport chain. When ROS exceed the antioxidant buffering capacity of tissues, oxidative stress occurs.
  • 1.0K
  • 15 Jun 2021
Topic Review
Age-Related Alterations at Neuromuscular Junction
With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes.
  • 800
  • 15 Jun 2021
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