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Topic Review
Atoh8 in Disease
Atoh8 is a transcription factor that belongs to a large superfamily of transcriptional regulators called bHLH proteins. In spite of two decades of research, multiple questions regarding its molecular function and involved mechanisms remain elusive.
  • 399
  • 29 Jan 2022
Topic Review
The Mitotic Spindle
During cell division, the mitotic spindle, a macromolecular structure primarily comprised of microtubules, drives chromosome alignment and partitioning between daughter cells. Mitotic spindles can sense cellular dimensions in order to adapt their length and mass to cell size.
  • 1.9K
  • 29 Jan 2022
Topic Review
Alternatively Spliced Isoforms in MAPK Signaling
The mitogen-activated protein kinase (MAPK) cascades are key signaling components  that transmit signals to many cellular processes. Each of the cascades operates by a sequential activation of protein kinases organized in three or more tiers that provide a seemingly linear signal transmission. However, the cellular effects regulated by each cascade may vary significantly. To achieve these diverse effects, the specificity of each cascade is extended by distinct regulators.  Here we describe the importance of having distinct components in each tier of the cascades, particularly alternatively spliced isoforms of the MAPK components. This mode of regulation extends the cascade’s specificity and allows accurate, fine-tuned signaling outcomes that lead to proper cell fates. 
  • 581
  • 28 Jan 2022
Topic Review
Redox-Regulation of α-Globin in Vascular Physiology
Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric oxide (NO) signaling with cellular oxygen availability and redox status. Small artery endothelial cells (ECs) express free α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe2+) α-globin to the oxidized (Fe3+) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe3+) α-globin must be stabilized and recycled to (Fe2+) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe3+) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe3+) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome b5 reductase (CyB5R3) with cytochrome b5 type A (CyB5a) can reduce (Fe3+) α-globin in solution.
  • 600
  • 28 Jan 2022
Topic Review
Human Anorectal Malformations
Anorectal malformations (ARM) represent a rare birth defect of the hindgut that occur in approximately 1 in 3000 live births. Around 60% of ARM occur with associated anomalies including defined genetic syndromes and associations with chromosomal aberrations. The etiology of ARM is heterogeneous, with the individual environmental or genetic risk factors remaining unknown for the majority of cases.
  • 216
  • 28 Jan 2022
Topic Review
Metabolic Alterations in Parkinson’s Disease
The PD model flies based on DJ-1β inactivation  exhibited protein metabolism alterations, a shift from the tricarboxylic acid cycle to glycolytic pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes. Thus, these metabolic changes could contribute to PD pathogenesis and might constitute possible therapeutic targets and/or biomarkers for this disease.
  • 444
  • 27 Jan 2022
Topic Review
STAT3 Enhances Sensitivity of Glioblastoma to Cell Death
Glioblastoma is the most common primary brain cancer in adults. One reason for the development and malignancy of this tumor is the misregulation of certain cellular proteins. The oncoprotein Signal Transducer and Activator of Transcription (STAT3) that is frequently overactive in glioblastoma cells is associated with more aggressive disease and decreased patient survival. Autophagy is a form of cellular self digestion that normally maintains cell integrity and provides nutrients and basic building blocks required for growth. While glioblastoma is known to be particularly resistant to conventional therapies, recent research has suggested that these tumors are more sensitive to excessive overactivation of autophagy, leading to autophagy-dependent tumor cell death.
  • 380
  • 26 Jan 2022
Topic Review
The H+ Transporter SLC4A11
Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H+ uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes.
  • 463
  • 25 Jan 2022
Topic Review
Fibrin Glue and MSCs to Regenerate Nerve Injuries
Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. Fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.
  • 471
  • 24 Jan 2022
Topic Review
CGF Biomolecules
Concentrated Growth Factors (CGF) represent new autologous (blood-derived biomaterial), attracting growing interest in the field of regenerative medicine. 
  • 264
  • 24 Jan 2022
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