[3] viXra:2011.0140 [pdf] submitted on 2020-11-19 19:04:04
Authors: Robyn A. Lindley, Edward J. Steele
Comments: 8 Pages.
In hepatocellular cancer (HCC) there is an over expression of the RNA editing enzyme ADAR1. Further, the prominent genomic somatic mutation signature in HCC is almost exclusively focused on mutations at A:T base pairs where A-to-G mutations far exceed T-to-C mutations (when read on the non-transcribed strand). A clear mechanism for this extreme transcriptional strand biased mutation signature, putatively associated with over expression of ADAR1 deaminase, is yet to be explicitly demonstrated. The standard description of this strand bias has been nominally called “Transcription Coupled Damage” (TCD) to distinguish it from more conventional “Transcription Coupled Repair” (TCR). We show that the TCD description does not satisfy all features of the molecular evidence. The conventional view is that ADAR1 is thought to target adenosines at WA-sites for editing to inosine (I) in double stranded RNA stem-loop structures in transcripts. Here we show that the totality of the molecular and cellular data on these mutation signatures provides strong presumptive evidence for a clear role for ADAR1-mediated A-to-I deamination at WA-sites as the mutagenic driver in hepatocellular and possibly other related ADAR1-Hi cancers displaying biased mutation features at A:T base pairs.
Category: Biochemistry
[2] viXra:2011.0006 [pdf] replaced on 2020-12-13 10:04:28
Authors: Wan-Chung Hu
Comments: 7 Pages.
Human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages, interferon gamma (IFNg) CD4 T cells, innate lymphoid cells 1 (ILC1), CD8 T cells, invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils, interleukin (IL)-22/IL-17 CD4 T cells, innate lymphoid cells 3 (ILC3), iNKT17 cells, and IgG2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), IL-5/IL-4 CD4 T cells, IL-25 inducing inflammatory innate lymphoid cells 2 (iILC2), mast cells-tryptase (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, mast cells-tryptase/chymase (MCtc), IL-3/IL-4 CD4 T cells, IL-33 inducing nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, IL-9 mast cells (MMC9), thymic stromal lymphopoietin inducing innate lymphoid cells 2, IL-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. This categorization provides a complete framework of immunological pathways against four types of parasitic infections.
Category: Biochemistry
[1] viXra:2011.0001 [pdf] submitted on 2020-11-01 09:50:32
Authors: Bezverkhniy Volodymyr Dmytrovych, Bezverkhniy Vitaliy Volodymyrovich
Comments: 6 Pages.
Since viruses are the first form of life on Earth, it can be shown that it was viruses that formed and spread biological life on the planet. The evolutionary transition from giant viruses to the first protozoan bacteria is logical and can be considered proven. The genome of the organism is encoded in DNA and viruses are the first form of life, therefore, in the past, there should have been the last universal DNA molecule, which contained the genes of all possible living beings in our biosphere.
Category: Biochemistry