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Topic Review
Nephronectin
Nephronectin (NPNT) was originally identified as an ECM protein by two independent research groups in 2001. Brandenberger et al. reported NPNT to be involved in the embryonic development of the kidney, hence the name nephronectin (nephron: unit within the kidney; nectin: cellular adhesion proteins). Morimura and colleagues discovered the same protein to be associated with osteoblast differentiation, and named it preosteoblast epidermal growth factor-like repeat protein with meprin, A5 protein and receptor protein-tyrosine phosphatase µ domain (POEM).
  • 1.1K
  • 08 Apr 2021
Topic Review
WNT Signaling
The WNT signaling pathway is an evolutionarily conserved signal transduction pathway that regulates a wide range of cellular functions during development and adulthood. It controls multiple aspects of development, including cell proliferation, cell fate determination, apoptosis, cell migration and cell polarity during development and stem cell maintenance in adults. Inappropriate activation of the WNT pathway is also a major factor in human oncogenesis.
  • 1.1K
  • 11 Mar 2022
Topic Review
Hyperinsulinaemia-Osteofragilitas
Bone fragility leading to increased risk of low energy (fragility) fractures that is independent of bone mineral density, occurring in individuals with detected and undetected hyperinsulinaemia. Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility “hyperinsulinaemia-osteofragilitas” phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures.  Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis.  Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.
  • 1.1K
  • 09 Oct 2021
Topic Review
Appendage Regeneration in Vertebrates
Appendage regeneration in vertebrates means the ability to regenerate amputated or injured tissues and organs, which is a fascinating property shared by several invertebrates and, interestingly, some vertebrates.
  • 1.1K
  • 01 Jun 2021
Topic Review
C. albicans
Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people.
  • 1.1K
  • 12 Aug 2021
Topic Review
GRKs
G protein-coupled receptor (GPCR) kinases (GRKs) play an important role in the regulation of signaling of GPCRs that bind neurotransmitters. The canonical model of GPCR desensitization posits that GRKs phosphorylate ligand-activated GPCRs, and this phosphorylation prepares receptors for the high-affinity binding of arrestin proteins. Arrestin binding prevents further G protein coupling, promotes receptor internalization, and initiates and/or facilitates specific branches of signaling. Existing data suggest that the role of GPCR phosphorylation by GRKs is distinct in different receptors. The relationship between G protein- and arrestin-mediated signaling on the one hand, and therapeutic and side effects of drugs on the other, is more complex than is widely believed. Also, the relationship between rapid (minutes to hours) GRK/arrestin-mediated regulation and long-term (days to weeks) neural plasticity remains to be elucidated. 
  • 1.1K
  • 19 Jan 2021
Topic Review
Organoids and Aging
The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.
  • 1.1K
  • 19 Oct 2021
Topic Review
Limb Development
The function of retinoic acid (RA) during limb development is still debated, as loss and gain of function studies led to opposite conclusions. With regard to limb initiation, genetic studies demonstrated that activation of FGF10 signaling is required for the emergence of limb buds from the trunk, with Tbx5 and RA signaling acting upstream in the forelimb field, whereas Tbx4 and Pitx1 act upstream in the hindlimb field. Early studies in chick embryos suggested that RA as well as Meis1 and Meis2 (Meis1/2) are required for subsequent proximodistal patterning of both forelimbs and hindlimbs, with RA diffusing from the trunk, functioning to activate Meis1/2 specifically in the proximal limb bud mesoderm. However, genetic loss of RA signaling does not result in loss of limb Meis1/2 expression and limb patterning is normal, although Meis1/2 expression is reduced in trunk somitic mesoderm. More recent studies demonstrated that global genetic loss of Meis1/2 results in a somite defect and failure of limb bud initiation. Other new studies reported that conditional genetic loss of Meis1/2 in the limb results in proximodistal patterning defects, and distal FGF8 signaling represses Meis1/2 to constrain its expression to the proximal limb.
  • 1.1K
  • 19 Jan 2021
Topic Review
The Role of Polyploidy in the Human Body
Somatic polyploidy was found in the tissues of all multicellular organisms (including algae, mosses, lichens, vascular plants, invertebrates, and vertebrates), which points to its adaptive value. In human and warm-blooded animals, polyploidy can be a part of normal postnatal morphogenetic programs and can be a manifestation of response to pathological stimuli and diseases.
  • 1.1K
  • 11 Apr 2022
Topic Review
Misregulation of Wnt Signaling Pathways
Wnt signaling pathways constitute a group of signal transduction pathways that direct many physiological processes, such as development, growth, and differentiation. Dysregulation of these pathways is thus associated with many pathological processes, including neurodegenerative diseases, metabolic disorders, and cancer. At the same time, alterations are observed in plasma membrane compositions, lipid organizations, and ordered membrane domains in brain and metabolic diseases that are associated with Wnt signaling pathway activation.
  • 1.1K
  • 03 Nov 2021
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