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Biography
Clemente Estable
Clemente Estable (23 May 1894, Canelones – 27 October 1976, Montevideo) was a University Professor and Docent. He was a pioneer in the areas of cellular biology and neurobiology research. Estable was an educator, scientist and philosopher who left his mark on the intellectual collective thinking of his native land. He lived his life guided by strong democratic values and ethical principles and
  • 1.3K
  • 01 Dec 2022
Topic Review
Wound Healing
Wound healing is a multistage dynamic process including haemostasis, inflammation, cell proliferation and tissue remodelling.
  • 1.3K
  • 09 Jul 2021
Topic Review
Epigenetic Regulation of PP2C Genes
The plant hormone abscisic acid (ABA) triggers cellular tolerance responses to osmotic stress caused by drought and salinity. ABA controls the turgor pressure of guard cells in the plant epidermis, leading to stomatal closure to minimize water loss. However, stomatal apertures open to uptake CO2 for photosynthesis even under stress conditions. ABA modulates its signaling pathway via negative feedback regulation to maintain plant homeostasis. In the nuclei of guard cells, the clade A type 2C protein phosphatases (PP2Cs) counteract SnRK2 kinases by physical interaction, and thereby inhibit activation of the transcription factors that mediate ABA-responsive gene expression. Under osmotic stress conditions, PP2Cs bind to soluble ABA receptors to capture ABA and release active SnRK2s. Thus, PP2Cs function as a switch at the center of the ABA signaling network. ABA induces the expression of genes encoding repressors or activators of PP2C gene transcription. These regulators mediate the conversion of PP2C chromatins from a repressive to an active state for gene transcription. The stress-induced chromatin remodeling states of ABA-responsive genes could be memorized and transmitted to plant progeny; i.e., transgenerational epigenetic inheritance.
  • 1.3K
  • 08 Jan 2021
Topic Review
Restoring Proliferation Competence in Terminally Differentiated Myotubes
Terminally differentiated cells are classically defined as specialized cells that have irreversibly lost their ability to proliferate (postmitotic state). Skeletal muscle myotubes are a model system to study terminal differentiation, more amenable than other terminally differentiated histotypes to experimental investigation. Arguably, the fundamental mechanisms underlying the postmitotic state should be shared by most TD cell types.
  • 1.3K
  • 19 Oct 2021
Topic Review
In Vitro Models of Immune Dysfunction in Space
Spaceflight affects the body on every level. Reports on astronaut health identify bone marrow remodelling and dysfunction of the innate immune system as significant health risks of long-term habitation in space. Microgravity-induced alterations of the bone marrow induce physical changes to the bone marrow stem cell niche. Downstream effects on innate immunity are expected due to impaired hematopoiesis and myelopoiesis. To date, few studies have investigated these effects in real microgravity and the sparsely available literature often reports contrasting results. This emphasizes a need for the development of physiologically relevant in vitro models of the bone marrow stem cell niche, capable of delivering appropriate sample sizes for robust statistics.
  • 1.3K
  • 07 Apr 2022
Topic Review
Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation
KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. In cancer cells, KRAS mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment.
  • 1.3K
  • 21 Jul 2022
Topic Review
MiR-615
miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It, therefore, serves as a biomarker for several types of cancer and recently has also been found to be involved in reparative processes and neural repair.
  • 1.3K
  • 27 Oct 2020
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.
  • 1.3K
  • 21 Jun 2021
Topic Review
Sublethal Cell Death Signaling
An important role of cell death pathways is to protect tissues and minimize disease by limiting the transference of potentially oncogenic mutations to daughter clones. However, there is increasing evidence demonstrating that activation of sublethal cell death signaling pathways, in particular apoptotic signaling, in the absence of direct DNA damaging stimuli, can promote genomic instability in cells that fail to die. This may increase the risk of the formation of subsequent neoplasms. Apoptosis-mediated mutagenesis occurs indirectly via sublethal activation of caspases and apoptotic nucleases (specifically CAD). On the other hand, cells surviving sublethal necroptotic signaling did not acquire mutations, most likely due to caspase-independent pathways, although the possibility of mutagenesis under conditions of oxidative stress are still elusive. It may therefore be possible for necroptosis-inducing anti-cancer drugs to be less likely than apoptosis-inducing or DNA damaging drugs to trigger therapy-related cancers.
  • 1.3K
  • 12 Jul 2021
Topic Review
Tunneling Nanotubes
Tunneling nanotubes (TNTs) are recognized long membrane nanotubes connecting distance cells. In the last decade, growing evidence has shown that these subcellular structures mediate the specific transfer of cellular materials, pathogens, and electrical signals between cells. As intercellular bridges, they play a unique role in embryonic development, collective cell migration, injured cell recovery, cancer treatment resistance, and pathogen propagation. Although TNTs have been considered as potential drug targets for treatment, there is still a long way to go to translate the research findings into clinical practice.
  • 1.3K
  • 10 Mar 2021
Topic Review
Membrane Remodeling by ESCRTs
The endosomal sorting complex required for transport (ESCRT) machinery is an evolutionarily conserved membrane remodeling complex that is used by the cell to perform reverse membrane scission in essential processes like protein degradation, cell division, and release of enveloped retroviruses. ESCRT-III, together with the AAA ATPase VPS4, harbors the main remodeling and scission function of the ESCRT machinery, whereas early-acting ESCRTs mainly contribute to protein sorting and ESCRT-III recruitment through association with upstream targeting factors.
  • 1.3K
  • 01 Jul 2022
Topic Review
Viral Infections in HNC
Head and neck cancers (HNC) occur in the upper aerodigestive tract and are among the most common cancers. The etiology of HNC is complex, involving many factors, including excessive tobacco and alcohol consumption. Over the last two decades, oncogenic viruses have also been recognized as an important cause of HNC. Major etiological agents of nasopharynx carcinoma and oropharyngeal carcinoma include Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), both of which are able to interfere with cell cycle control. Additionally, the association of hepatitis C and hepatitis B infection was observed in oral cavity, oropharyngeal, laryngeal, and nasopharyngeal cancers. Overall prognoses depend on anatomic site, stage, and viral status. Current treatment options, including radiotherapy, chemotherapy, targeted therapies and immunotherapies, are distributed in order to improve overall patient prognosis and survival rates. However, the interplay between viral genome sequences and the health, disease, geography, and ethnicity of the host are crucial for understanding the role of viruses and for development of potential personalized treatment and prevention strategies.
  • 1.3K
  • 22 Sep 2021
Topic Review
Human Neuroblastoma Cell
Neuroblastoma is one of the most common childhood solid tumors and develops from neural stem cells that normally comprise the embryonic structure termed the neural crest. Human neuroblastoma cell lines have special properties as they exhibit cell growth and are induced to become mature neurons by drugs such as retinoid.
  • 1.3K
  • 21 Oct 2021
Topic Review
Temozolomide Use in IDH-Mutant Gliomas
In this entry, we discuss the use of the alkylating agent temozolomide (TMZ) in the treatment of IDH-mutant gliomas. We describe the challenges associated with TMZ in clinical (drug resistance and tumor recurrence) and preclinical settings (variabilities associated with in vitro models) in treating IDH-mutant glioma.
  • 1.3K
  • 03 Jun 2021
Topic Review
PBK/TOPK: A Therapeutic Target
T-lymphokine-activated killer cell-originated protein kinase (TOPK), also known as PDZ-binding kinase (PBK), was a member of the MEK3/6-related MAPKK family. As a mitotic serine/threonine protein kinase, accumulating evidence supported its role in mitosis and cell-cycle progression of mitotically active cells, especially proliferative malignant cells. PBK/TOPK was confirmed to be associated with the development, progression, and metastasis of malignancies, which made it a potential therapeutic target in cancer therapy. Further, it was also demonstrated to play crucial roles in ischemic injury and involve in protection against ischemia. This protective effect of PBK/TOPK in the context of ischemia challeged the development of PBK/TOPK inhibitors in anti-tumor therapy, and more research was required to further explore its role and underlying mechanisms to translate its application to clinical studies.  
  • 1.3K
  • 20 Mar 2021
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.
  • 1.3K
  • 22 Jun 2021
Topic Review
Homologous Recombination Repair Deficiency
Homologous recombination repair deficiency (HRD) can be observed in virtually all cancer types. Cells possess a complex set of non-redundant and partially overlapping pathways to detect and repair DNA damage. In cancer, DNA damage repair (DDR) is frequently disrupted, leading to genomic instability. One of the pathways that is regularly altered in cancer is HR. HR is an important pathway for the repair of double-strand DNA breaks (DSBs) during the S and G2 phase of the cell cycle, i.e., after DNA replication has occurred. HR is considered a relatively error-free process because it uses an intact sister chromatid to guide DNA repair. HR deficiency (HRD) leads to enhanced reliance on alternative pathways involved in DSB repair, i.e., classical NHEJ, alternative end joining, and single-strand annealing. These pathways repair DSBs without a homologous DNA template, resulting in characteristic genomic scars across the genome.
  • 1.3K
  • 25 May 2021
Topic Review
Hyperthermia
Hyperthermia is one of the severe acute adverse effects that can be caused by the ingestion of recreational drugs, such as methcathinones. The effect of hyperthermia on neurotoxicity is currently not known. The primary aim of our study was therefore to investigate the effects of hyperthermia (40.5 °C) on the neurotoxicity of methcathinone (MC), 4-chloromethcathinone (4-CMC), and 4-methylmethcathinone (4-MMC) in SH-SY5Y cells. We found that 4-CMC and 4-MMC were cytotoxic (decrease in cellular ATP and plasma membrane damage) under both hyper- (40.5 °C) and normothermic conditions (37 °C), whereby cells were more sensitive to the toxicants at 40.5 °C. 4-CMC and 4-MMC impaired the function of the mitochondrial electron transport chain and increased mitochondrial formation of reactive oxygen species (ROS) in SH-SY5Y cells, which were accentuated under hyperthermic conditions. Hyperthermia was associated with a rapid expression of the 70 kilodalton heat shock protein (Hsp70), which partially prevented cell death after 6 h of exposure to the toxicants. After 24 h of exposure, autophagy was stimulated by the toxicants and by hyperthermia but could only partially prevent cell death. In conclusion, hyperthermic conditions increased the neurotoxic properties of methcathinones despite the stimulation of protective mechanisms. These findings may be important for the understanding of the mechanisms and clinical consequences of the neurotoxicity associated with these compounds.
  • 1.3K
  • 29 Oct 2020
Topic Review
Functional Roles of ISG15/ISGylation in Cancer
The protein ISG15 encoded by interferon-stimulated gene (ISG) 15 is the first identified member of the ubiquitin-like protein family and exists in the form of monomers and conjugated complexes. Like ubiquitin, ISG15 can mediate an ubiquitin-like modification by covalently modifying other proteins, known as ISGylation. There is growing evidence showing that both the free and conjugated ISG15 are involved in multiple key cellular processes, including autophagy, exosome secretion, DNA repair, immune regulation, and cancer occurrence and progression.
  • 1.3K
  • 17 Feb 2023
Topic Review
Insights into HP1a-Chromatin Interactions
     Understanding the packaging of DNA into chromatin is essential for the study of gene expression regulatory mechanisms. Heterochromatin establishment and maintenance dynamics have emerged as key features involved in genome stability, cellular growth, and disease. The heterochromatin protein HP1a is the most extensively studied factor that has both establishment and heterochromatin maintenance activities. This protein has two primary domains, namely the chromoshadow and the chromodomain, separated by a hinge region. Several works have taken place over the years, taking the challenge of defining HP1a partners using diverse experimental approaches. We revised and assemble on explaining these interactions and the potential complexes and subcomplexes associated formed with this essential protein. Characterization of these complexes will allow us to clearly understand the consequences of HP1a interactions in heterochromatin in maintenance, heterochromatin dynamics, and the direct relationship of heterochromatin with gene regulation.
  • 1.3K
  • 03 Apr 2021
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