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The biology of parasites from the genus Argulus and a review of the interactions with its host
Published in G. F. Wiegertjes, G. Flik, Host-Parasite Interactions, 2004
Peter D. Walker, Gert Flik, Sjoerd E. Wendelaar Bonga
The physiological mechanisms of the teleost-integrated stress response have been shown to share many similarities with that of terrestrial vertebrates (Wendelaar Bonga, 1997). The responses exhibited by a fish subjected to a stressor will involve physiological and behavioural responses that are induced as mechanisms to try and protect homeostasis or maintain the dynamic equilibrium of the stressed organism (Wendelaar Bonga, 1997). These responses have been categorized by previous authors as primary, secondary and tertiary responses.
Analysis of single-cell sequencing results of an elderly patient with myeloid leukemia reveals high expression of multiple oncogenes in monocytes and hematopoietic stem cells
Published in Hematology, 2023
Xiaoli Xu, Minjian Xiong, Haiyan Ye, Yonglei Qi, Ying Zhao
We further analyzed the pathways enrichment of HSCs and compared peripheral blood with bone marrow (Figure 4(E–H)). Results of GO showed that the pathways correlated with the biological process were PERK-mediated unfolded protein response, integrated stress response signaling, negative regulation of phosphorylation, regulation of hemopoiesis, and cellular response to the biotic stimulus. The pathways correlated with cellular components were nuclear specks. The pathways correlated with molecular functions were ubiquitin protein ligase binding, ubiquitin-like protein ligase binding, protein kinase regulator activity, nuclear hormone receptor binding, and hormone receptor binding. Results of KEGG showed that several pathways related to malignancy were active in peripheral blood HSCs, such as the MAPK signaling pathway, transcriptional mis-regulation in cancer, and TNF signaling pathway. Figure 5(D) and (E) shows the network of DEGs in pathways of biological processes and molecular functions. Some genes formed key nodes linking various pathways, such as JUN, PPP1R15B, and PRKAR1A.
A patent review of pharmaceutical and therapeutic applications of oxadiazole derivatives for the treatment of chronic diseases (2013–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Abbas Hassan, Abid Hussain Khan, Faiza Saleem, Haseen Ahmad, Khalid Mohammed Khan
Integrated Stress Response (ISR) is a cellular stress response that helps cells, tissues, and organisms to adapt to a variable environment to maintain healthy conditions. ISR restores the imbalance caused by pathological conditions such as viral infection, oxidative stress, nutrition deprivation, and homeostasis. Four different kinase families are responsible for the phosphorylation of the translation initiation factor 2 alpha (eIF2α) which leads to a decrease in protein synthesis. Upregulation of ISR has been linked to various conditions including cancer and neurodegenerative disease. Therefore, the ISR signaling may represent an effective treatment of some sort of cancer by the anti-proliferation strategy. In addition, ISR signaling may be effective in preserving synaptic function and reducing neuronal decline. This can help in Alzheimer’s disease, Jakob Creutzfeldt disease, and Parkinson’s disease. Atton et al. reported that 1,2,4-oxadiazole derivative appendant of chiral piperidine ring has shown excellent activity. The compounds were screened to prevent tunicamycin-induced ISR in wild-type human embryonic kidney (HEK-293) cells (Figure 58). Most of the compounds 195–198 showed IC50 values below 50 nM [128].
Isocaloric low protein diet in a mouse model for vanishing white matter does not impact ISR deregulation in brain, but reveals ISR deregulation in liver
Published in Nutritional Neuroscience, 2022
Lisanne E. Wisse, Denise Visser, Timo J. ter Braak, Abdellatif Bakkali, Eduard A. Struys, Christopher D. Morrison, Marjo S. van der Knaap, Truus E. M. Abbink
Vanishing white matter (VWM) is a chronic progressive neurological disease with rapid worsening of the disease provoked by stressors, especially febrile infections.1,2 Progression of the chronic disease is inversely correlated with the age of onset.3 VWM is caused by mutations in any of the five subunits of eIF2B with a reported genotype-phenotype correlation.3,4 eIF2B is essential for the protein synthesis and is a key factor of the integrated stress response (ISR).5 This ISR is activated by various types of proteotoxic stimuli, each activating a kinase that phosphorylates the α subunit of eIF2, e.g. protein kinase R (PKR) activated by viral infections, or general control non-derepressible 2 (GCN2) by shortage of amino acids.6 Phosphorylated eIF2 reduces eIF2B activity,5 which decreases general protein synthesis rates, yet increases the synthesis of specific proteins such as the transcription factor ATF4.7,8 These specific proteins induce a change in the transcription profile as a part of the ISR.6 Expression of this 'ISR transcriptome' is initially aimed to protect cells and restore proteostasis, but leads to cell death when the stress is long lasting or severe.