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Topic Review
Regulation of Hedgehog Signal Transduction
The Hedgehog (Hh) family of secreted proteins governs embryonic development and adult tissue homeostasis in species ranging from insects to mammals. Deregulation of Hh pathway activity has been implicated in a wide range of human disorders, including congenital diseases and cancer. Hh exerts its biological influence through a conserved signaling pathway. Binding of Hh to its receptor Patched (Ptc), a twelve-span transmembrane protein, leads to activation of an atypical GPCR family protein and Hh signal transducer Smoothened (Smo), which then signals downstream to activate the latent Cubitus interruptus (Ci)/Gli family of transcription factors. Hh signal transduction is regulated by ubiquitination and deubiquitination at multiple steps along the pathway including regulation of Ptc, Smo and Ci/Gli proteins. 
  • 664
  • 15 Dec 2021
Topic Review
Autonomy in Stem Cell-Derived Embryoids
The experimental production of complex structures resembling mammalian embryos (e.g., blastoids, gastruloids) from pluripotent stem cells in vitro has become a booming research field. Since some of these embryoid models appear to reach a degree of complexity that may come close to viability, a broad discussion has set in with the aim to arrive at a consensus on the ethical implications with regard to acceptability of the use of this technology with human cells. The present text focuses on developmental autonomy of embryoids which is an aspect of great ethical relevance and must receive increased attention during the preparation of new legal regulations, but which has not been included yet in the recently issued ISSCR Guidelines.  
  • 655
  • 10 Nov 2021
Topic Review Video
Transgenerational-Epigenetic Inheritance and Immune System
Epigenetic modifications cause heritable changes in gene expression which are not due to alterations in underlying DNA sequence. Inside the eukaryotic nucleus, there is condense packing of DNA around histone proteins to constitute chromatin structure. Epigenetic modifications are caused by factors that alter chromatin structure. Some epigenetic factors are enzymes that regulate DNA methylation and histone modifications, non-coding RNA, and prions. An offspring inherits parental epigenetic modifications but most of them are deleted and reset during early developmental stages. Some epigenetic modifications are retained and persist across multiple generations. If any epigenetic modification is the result of a stimulus or immune response in one generation, such that the modification continues to be inherited in subsequent generations which are not subjected to the stimulus; and the inheritance continues beyond the 3rd generation in the female germline and 2nd generation in male, then the phenomenon is called transgenerational epigenetic inheritance (TGEI). This entry is focused on a review which discusses some examples of TGEI that are reported in association with  immune system development and disorders.
  • 652
  • 22 May 2021
Topic Review
Autosomal Dominant Lateral Temporal Epilepsy
Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy associated with mutations in the LGI1, RELN, and MICAL1 genes. A previous study linking ADLTE with two MICAL1 mutations that resulted in the substitution of a highly conserved glycine residue for serine (G150S) or a frameshift mutation that swapped the last three C-terminal amino acids for 59 extra residues (A1065fs) concluded that the mutations increased enzymatic activity and promoted cell contraction.
  • 652
  • 11 May 2022
Topic Review
Development of Schwann Cells
Schwann cells are glial cells of the peripheral nervous system. They exist in several subtypes and perform a variety of functions in nerves. Their derivation and culture in vitro are interesting for applications ranging from disease modeling to tissue engineering. Since primary human Schwann cells are challenging to obtain in large quantities, in vitro differentiation from other cell types presents an alternative. To achieve differentiation of Schwann cells from stem cell sources in vitro, cultures are manipulated using molecular factors to emulate developmental signaling events which lead to development of Schwann cells in vivo. Therefore, knowledge of molecular determinants in embryonal development of the Schwann cell fate is key to develop and refine in vitro differentiation protocols.
  • 651
  • 05 Dec 2022
Topic Review
The Double Homeobox Gene
The double homeobox (Dux) gene, encoding a double homeobox transcription factor, is one of the key drivers of totipotency in mice. Recent studies showed Dux was temporally expressed at the 2-cell stage and acted as a transcriptional activator during zygotic genome activation (ZGA) in embryos. A similar activation occurs in mouse embryonic stem cells, giving rise to 2-cell-like cells (2CLCs). Though the molecular mechanism underlying this expanded 2CLC potency caused by Dux activation has been partially revealed, the regulation mechanisms controlling Dux expression remain elusive.
  • 633
  • 17 Feb 2022
Topic Review
Congenital Lung Malformations
Congenital lung malformations arise during development and include numerous anatomical anomalies of the lung and respiratory tree. They are usually detected prenatally by ultrasonography and comprise congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration (BPS), bronchogenic cysts (BC), and more rarely bronchial atresia, congenital lobar emphysema (CLE), and congenital tracheal obstruction. This entry focuses on the molecular and genetic determinants of the most frequent anomalies: CPAM, BPS, and BC. Congenital diaphragmatic hernia (CDH) is not usually included in this group; however, since the lung is also highly affected in this condition, we have also incorporated evidence related to lung hypoplasia.
  • 620
  • 30 Nov 2021
Topic Review
Epigenetic Regulation of the β-Globin Genes
Beta-like globin gene expression is developmentally regulated during life by transcription factors, chromatin looping and epigenome modifications of the β-globin locus. Epigenome modifications, such as histone methylation/demethylation and acetylation/deacetylation and DNA methylation, are associated with up- or down-regulation of gene expression. The understanding of these mechanisms and their outcome in gene expression has paved the way to the development of new therapeutic strategies for treating various diseases, such as β-hemoglobinopathies.
  • 615
  • 06 Mar 2023
Topic Review
Aperture Formation in Angiosperms
Apertures are the areas where the exine is thinner or even lacking. A great diversity in pollen grain morphology is observed in angiosperms.
  • 613
  • 18 Feb 2022
Topic Review
Physiological Role of Mitogen-Activated Protein Kinase in Eye
Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life (such as development of eye) and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. 
  • 603
  • 08 Mar 2023
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