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Topic Review
Casein Kinase 1α
Wnt signaling regulates numerous cellular processes during embryonic development and adult tissue homeostasis. Underscoring this physiological importance, deregulation of the Wnt signaling pathway is associated with many disease states, including cancer. Here, we review pivotal regulatory events in the Wnt signaling pathway that drive cancer growth. We then discuss the roles of the established negative Wnt regulator, casein kinase 1α (CK1α), in Wnt signaling. Although the study of CK1α has been ongoing for several decades, the bulk of such research has focused on how it phosphorylates and regulates its various substrates. We focus here on what is known about the mechanisms controlling CK1α, including its putative regulatory proteins and alternative splicing variants. Finally, we describe the discovery and validation of a family of pharmacological CK1α activators capable of inhibiting Wnt pathway activity. One of the important advantages of CK1α activators, relative to other classes of Wnt inhibitors, is their reduced on-target toxicity, overcoming one of the major impediments to developing a clinically relevant Wnt inhibitor. Therefore, we also discuss mechanisms that regulate CK1α steady-state homeostasis, which may contribute to the deregulation of Wnt pathway activity in cancer and underlie the enhanced therapeutic index of CK1α activators. 
  • 985
  • 26 Oct 2020
Biography
Nicolas-Théodore de Saussure
Nicolas-Théodore de Saussure (14 October 1767, in Geneva – 18 April 1845, in Geneva [1]) was a Switzerland chemist and student of plant physiology who made seminal advances in phytochemistry. He is one of the major pioneers in the study of photosynthesis.[2] Nicolas-Théodore de Saussure was born into a wealthy, aristocratic, Genevan family, many of whose members were accomplished in the n
  • 984
  • 15 Nov 2022
Topic Review
Voltage-Gated K+ Channels
Voltage-gated K+ (Kv) channels are intrinsic plasma membrane proteins mediating the selective flow of potassium ions in response to depolarization of the transmembrane electric field. Their ionic selectivity and voltage dependence allow Kv channels to be central players in virtually all physiological functions, including the maintenance and modulation of neuronal and muscular (both cardiac and skeletal) excitability, regulation of calcium signaling cascades, control of cell volume, immune response, hormonal secretion, and others.
  • 984
  • 29 Jan 2022
Topic Review
Antimicrobial Peptides Synergy with Vancomycin
There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.
  • 984
  • 29 Oct 2020
Topic Review
Tenascin-C-Derived Peptide, TNIIIA2
Matricellular proteins harbor functional sites within their molecular structures. These functional sites are released via proteolytic cleavage by inflammatory proteinases, and the peptides containing these hidden functional sites have unique biological activities that are often not detected in the parent molecules. A peptide containing the functional site of tenascin-C (TNC), termed TNIIIA2, which is highly released at sites of inflammation and in the tumor microenvironment, has the ability to potently and persistently activate β1-integrins. Based on these activities, TNIIIA2-containing TNC fragments/peptides are involved in the acquisition of aggressiveness in cancer progression.
  • 984
  • 09 Nov 2020
Topic Review
Parkinson’s genes in neurological disorders
Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Several genes and genomic regions are highlighted, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence the development of both ASD and PD, with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes, which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches.
  • 984
  • 24 Aug 2020
Biography
William Thomson, Baron Kelvin
William Thomson, Baron Kelvin, OM, GCVO, PC, PRS, FRSE (26 June 1824 – 17 December 1907) was a British[1] mathematical physicist and engineer who was born in Belfast in 1824. At the University of Glasgow he did important work in the mathematical analysis of electricity and formulation of the first and second laws of thermodynamics, and did much to unify the emerging discipline of physics in it
  • 984
  • 01 Dec 2022
Topic Review
Metal Tolerance Protein
Metal tolerance proteins (MTPs) are plant divalent cation transporters that play important roles in plant metal tolerance and homeostasis. Poplar is an ideal candidate for the phytoremediation of heavy metals because of its numerous beneficial attributes. Here, 22 MTP genes in P. trichocarpa were identified and classified into three major clusters and seven groups according to phylogenetic relationships. An evolutionary analysis suggested that PtrMTP genes had undergone gene expansion through tandem or segmental duplication events. Moreover, all PtrMTPs were predicted to localize in the vacuole and/or cell membrane, and contained typical structural features of the MTP family, cation efflux domain. The temporal and spatial expression pattern analysis results indicated the involvement of PtrMTP genes in poplar developmental control. Under heavy metal stress, most of PtrMTP genes were induced by at least two metal ions in roots, stems or leaves. In addition, PtrMTP8.1, PtrMTP9 and PtrMTP10.4 displayed the ability of Mn transport in yeast cells, and PtrMTP6 could transport Co, Fe and Mn. These findings will provide an important foundation to elucidate the biological functions of PtrMTP genes, and especially their role in regulating heavy metal tolerance in poplar.
  • 984
  • 26 Oct 2020
Topic Review
MYC
Despite the advancements in cancer treatments, gastric cancer is still one of the leading causes of death worldwide. In this context, it is of great interest to discover new and more effective ways of treating this disease. Accumulated evidences have demonstrated the amplification of 8q24.21 region in gastric tumors. Furthermore, this is the region where the widely known MYC oncogene and different microRNAs are located. MYC deregulation is key in tumorigenesis in various types of tissues, once it is associated with cell proliferation, survival, and drug resistance. microRNAs are a class of noncoding RNAs that negatively regulate the protein translation, and which deregulation is related with gastric cancer development. However, little is understood about the interactions between microRNAs and MYC. Here, we overview the MYC role and its relationship with the microRNAs network in gastric cancer aiming to identify potential targets useful to be used in clinic, not only as biomarkers, but also as molecules for development of promising therapies.
  • 984
  • 27 Oct 2020
Topic Review
Astrocytes as Templates for Angiogenesis
 Angiogenesis is a key process in various physiological conditions in the nervous system and in the retina during postnatal life. Although an increasing number of studies have addressed the role of endothelial cells in this event, the astrocytes contribution in angiogenesis has received less attention.
  • 984
  • 08 Apr 2022
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