scholarly journals Corrigendum to “Trichloroethene degradation by nanoscale CaO2 activated with Fe(II)/FeS: The role of FeS and the synergistic activation mechanism of Fe(II)/FeS” [Chem. Eng. J. 394 (2020) 124830]

2022 ◽  
Vol 428 ◽  
pp. 131394
Author(s):  
Yong Sun ◽  
Muhammad Danish ◽  
Meesam Ali ◽  
Ali Shan ◽  
Ming Li ◽  
...  
Keyword(s):  
Activation Mechanism ◽  
Synergistic Activation

Trichloroethene degradation by nanoscale CaO2 activated with Fe(II)/FeS: The role of FeS and the synergistic activation mechanism of Fe(II)/FeS

2020 ◽  
Vol 394 ◽  
pp. 124830 ◽  
Author(s):  
Yong Sun ◽  
Muhammad Danish ◽  
Meesam Ali ◽  
Ali Shan ◽  
Ming Li ◽  
...  
Keyword(s):  
Activation Mechanism ◽  
Synergistic Activation

STRUCTURAL COMPONENTS OF THE PRIVATE MEDICAL SECTOR ACTIVATION MECHANISM

Economical ◽  
2019 ◽  
Vol 2 (2(21)) ◽  
pp. 170-177
Author(s):  
Anzhela Bairak ◽  
Keyword(s):  
Health Care ◽  
Health Care System ◽  
Activation Mechanism ◽  
Practical Significance ◽  
Structural Components ◽  
Medical Sector ◽  
Analysis And Synthesis ◽  
Private Medicine ◽  
Care System

The article examines the problems of private medicine in the health care system of the country. The aim of the article is to determine the structural components of the mechanism of activation of the private medical sector as a reserve for the provision of quality and affordable medical services and a driver for the development of the medical industry. The descriptive-analytical method, methods of analysis and synthesis, comparison, statistical, analysis and scientific generalization were used in the paper. The study substantiates the strengthening of the role of the private medical sector in the health care management system. The key problems of the domestic private medical sector and the restraining factors of its development are identified. It is concluded that it is necessary to develop a mechanism to promote the development of private medicine through a policy of active change in the health care system. The directions of activation of the private medical sector as a target reference point in the process of determining the structural elements of the organizational and economic mechanism are outlined. The structural detail of the mechanism of activation of the private medical sector for optimization of the health care system is offered. The practical significance of the obtained results is that the results of the research presented in the article are a practical basis for the development and improvement of mechanisms of public administration in the field of health care.

scholarly journals PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling

2021 ◽  
Vol 22 (10) ◽  
pp. 5112
Author(s):  
Lotte van Beek ◽  
Éilís McClay ◽  
Saleha Patel ◽  
Marianne Schimpl ◽  
Laura Spagnolo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Parp Inhibitors ◽  
Covalent Modification ◽  
Activation Mechanism ◽  
Cancer Therapies ◽  
Damage Repair ◽  
Complementary Role ◽  
Functional Understanding

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central to the important functions of PARP enzymes in the DNA damage response and nucleosome remodelling. Activation of PARP happens through DNA binding via zinc fingers and/or the WGR domain. Modulation of their activity using PARP inhibitors occupying the NAD+ binding site has proven successful in cancer therapies. For decades, studies set out to elucidate their full-length molecular structure and activation mechanism. In the last five years, significant advances have progressed the structural and functional understanding of PARP1-3, such as understanding allosteric activation via inter-domain contacts, how PARP senses damaged DNA in the crowded nucleus, and the complementary role of histone PARylation factor 1 in modulating the active site of PARP. Here, we review these advances together with the versatility of PARP domains involved in DNA binding, the targets and shape of PARylation and the role of PARPs in nucleosome remodelling.

scholarly journals Activation mechanism of ATP-sensitive K+ channels explored with real-time nucleotide binding

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Michael Puljung ◽  
Natascia Vedovato ◽  
Samuel Usher ◽  
Frances Ashcroft
Keyword(s):  
Conformational Change ◽  
Ionic Currents ◽  
Nucleotide Binding ◽  
Activation Mechanism ◽  
Time Resolved ◽  
K Channels ◽  
Novel Approach ◽  
Binding Event ◽  
Fluorescent Nucleotides

The response of ATP-sensitive K+ channels (KATP) to cellular metabolism is coordinated by three classes of nucleotide binding site (NBS). We used a novel approach involving labeling of intact channels in a native, membrane environment with a non-canonical fluorescent amino acid and measurement (using FRET with fluorescent nucleotides) of steady-state and time-resolved nucleotide binding to dissect the role of NBS2 of the accessory SUR1 subunit of KATP in channel gating. Binding to NBS2 was Mg2+-independent, but Mg2+ was required to trigger a conformational change in SUR1. Mutation of a lysine (K1384A) in NBS2 that coordinates bound nucleotides increased the EC50 for trinitrophenyl-ADP binding to NBS2, but only in the presence of Mg2+, indicating that this mutation disrupts the ligand-induced conformational change. Comparison of nucleotide-binding with ionic currents suggests a model in which each nucleotide binding event to NBS2 of SUR1 is independent and promotes KATP activation by the same amount.

Synergistic activation of mitogen-activated protein kinase by insulin and adenosine triphosphate in liver cells: Permissive role of Ca2+

Metabolism ◽  
2003 ◽  
Vol 52 (5) ◽  
pp. 590-598 ◽  
Author(s):  
Pierre S. Haddad ◽  
Diane Vallerand ◽  
Laurence Mathé ◽  
Kenza Benzeroual ◽  
Gérald Van de Werve
Keyword(s):  
Protein Kinase ◽  
Adenosine Triphosphate ◽  
Liver Cells ◽  
Mitogen Activated Protein Kinase ◽  
Synergistic Activation ◽  
Mitogen Activated Protein ◽  
Permissive Role

scholarly journals Activation of the miR-371/372/373 miRNA Cluster Enhances Oncogenicity and Drug Resistance in Oral Carcinoma Cells

2020 ◽  
Vol 21 (24) ◽  
pp. 9442
Author(s):  
Shu-Chun Lin ◽  
Hsiao-Li Wu ◽  
Li-Yin Yeh ◽  
Cheng-Chieh Yang ◽  
Shou-Yen Kao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcriptional Activation ◽  
Mirna Cluster ◽  
Human Stem Cells ◽  
Oncogenic Potential ◽  
Synergistic Activation ◽  
Cisplatin Sensitivity ◽  
The Individual ◽  
Cell Subclones

Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated deaths worldwide. Family members in miR-371/372/373 miRNA cluster, which is localized at human chromosome 19q13.4, are co-expressed in both human stem cells and malignancies. The individual miRNA in this cluster are also involved in modulating the pathogenesis of malignancies as either oncogenes or suppressors. The 19q13 region is frequently gained in head and neck cancers. High expression of miR-372 and miR-373 are survival predictors for OSCC. However, the role of the miR-371/372/373 cluster in oral carcinogenesis remains to be fully investigated. We use the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system to establish OSCC cell subclones that had the miR-371/372/373 cluster deleted. In addition, further subclones were established that had the promoter of this cluster deleted. Concordant silencing in SAS cells of miR-371/372/373 decreased oncogenic potential, increased cisplatin sensitivity, activated p53, and upregulated the expression of Bad and DKK1. We also employed the CRISPR/dCas9 synergistic activation mediator system, which allowed robust transcriptional activation of the whole miR-371/372/373 cistron. Upregulation of endogenous miR-371/372/372 expression increased both oncogenicity and drug resistance. These were accompanied by a slight activation of AKT, β-catenin, and Src. This study identifies the oncogenic role of the miR-371/372/373 cluster in OSCC. Using CRISPR based strategy can be a powerful paradigm that will provide mechanistic insights into miRNA cluster functionality, which will also likely help the development of targeting options for malignancies.

scholarly journals An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases

2021 ◽  
Vol 22 (17) ◽  
pp. 9592
Author(s):  
Emilia Zgorzynska ◽  
Barbara Dziedzic ◽  
Anna Walczewska
Keyword(s):  
Leucine Zipper ◽  
Target Genes ◽  
Protective Efficacy ◽  
Antioxidant Response ◽  
Activation Mechanism ◽  
Age Related ◽  
Nrf2 Activation ◽  
Metabolic Conditions ◽  
Lateral Sclerosis

Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions. After synthesis, Nrf2 is arrested in the cytoplasm by the Kelch-like ECH-associated protein 1 suppressor (Keap1) leading Nrf2 to ubiquitin-dependent degradation. One Nrf2 activation mechanism relies on disconnection from the Keap1 homodimer through the oxidation of cysteine at specific sites of Keap1. Free Nrf2 enters the nucleus, dimerizes with small musculoaponeurotic fibrosarcoma proteins (sMafs), and binds to the antioxidant response element (ARE) sequence of the target genes. Since oxidative stress, next to neuroinflammation and mitochondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies, a molecular intervention into Nrf2/ARE signaling and the enhancement of the transcriptional activity of particular genes are targets for prevention or delaying the onset of age-related and inherited neurogenerative diseases. In this study, we review evidence for the Nrf2/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.

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