The radiation-induced bystander effect (RIBE) is the initiation of biological end points in cells (bystander cells) that are not directly traversed by an incident-radiation track, but are in close proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS) act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to pursue this field of science.
Bilateral frontoparietal polymicrogyria (BFPP, MIM 606854) is a heterogeneous autosomal recessive disorder of abnormal cortical lamination, leading to moderate-to-severe intellectual disability (ID), seizure disorder, and motor difficulties, and caused by mutations in the G protein-coupled receptor 56 ( ) gene. Twenty-eight mutations in 40 different families have been reported in the literature. The clinical and neuroimaging phenotype is consistent in these cases. The BFPP cortex consists of numerous small gyral cells, with scalloping of the cortical-white matter junction. There are also associated white matter, brain stem, and cerebellar changes. is a member of an adhesion G protein-coupled receptor family with a very long N-terminal stalk and seven transmembrane domains. In this study, we identified three families from Pakistan, ascertained primarily for ID, with overlapping approximately 1 Mb region (chr16:56,973,335-57,942,866) of homozygosity by descent, including 24 RefSeq genes. We found three homozygous mutations, using next-generation sequencing. These mutations include a substitutional variant, c.1460T> C; p.L487P, (chr16:57693480 T > C), a 13-bp insertion causing the frameshift and truncating mutation, p.Leu269Hisfs*21 (NM_005682.6:c.803_804insCCATGGAGGTGCT; Chr16: 57689345_57689346insCCATGGAGGTGCT), and a truncating mutation c.1426C > T; p.Arg476* (Chr16:57693446C > T). These mutations fully segregated with ID in these families and were absent in the Exome Aggregation Consortium database that has approximately 8,000 control samples of South Asian origin. Two of these mutations have been reported in ClinVar database, and the third one has not been reported before. Three families from Pakistan with mutations have been reported before. With the addition of our findings, the total number of mutations reported in Pakistani patients now is six. These results increase our knowledge regarding the mutational spectrum of the gene causing BFPP/ID.
Protein modelling plays a vital role in the drug discovery process. TANK-binding kinase 1–binding protein 1 is also called an adapter protein, which is encoded by gene TBK1 present in Homo sapiens. It is found in lungs, small intestine, leukocytes, heart, placenta, muscle, kidney, lower level of thymus, and brain. It has a number of protein-binding sites, to which TBK1 and IKBKE bind and perform different functions as immunomodulatory, antiproliferative, and antiviral innate immunity which release different types of interferons. Our study predicts the comparative model of 3-dimensional (3D) structure through different bioinformatics tools that will be helpful for further studies in future. The reactivity and stability of these proteins were evaluated physicochemically and through domain determination and prediction of secondary structure using bioinformatics methods such as ProtParam, Pfam, and SOPMA, respectively. Robetta, an ab initio approach, I-TASSER, and AlphaFold was used for 3D structure prediction, and the models were validated using the SAVESv6.0 (PROCHECK) server. Conclusively, the best 3D structure of TBK1-binding protein 1 was predicted using Robetta software. After unveiling the 3D structure of the novel protein, we concluded that this structure will help us to find out its role other than in antiviral innate immunity and by producing torsion in its 3D structure researchers will be able to detect either this protein is involved in any disease or not because according to previous studies it was not associated with any disease.
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