Biology subjects

Nowak, E.

Publications and source records attributed to Nowak, E..

3 recordsLinked to original sources

bioRxiv2023

RNA 5' terminal nucleotide determines the strength of the RIG-I/IFN signaling pathway

The interferon (IFN) response is crucial for antiviral activity, but its overstimulation can lead to a wide range of autoimmune disorders. The cytoplasmic pattern recognition receptor RIG-I detects viral double-stranded RNAs (dsRNAs) and endogenous polymerase III transcripts carrying a 5'-triphosphate (5'-ppp) or 5'-diphosphate (5'-pp) moiety, triggering phosphorylation of IRF3 and IFN immune response. While many viral RNAs initiate with 5'-ppp-adenosine (5'-pppA) and most endogenous Pol III transcripts in higher eukaryotes start with 5'-ppp-guanosine (5'-pppG), no apparent reason for this bias has been identified so far. Here we demonstrate that dsRNAs initiating with 5'-pppA trigger stronger RIG-I/IFN response than those starting with 5'-pppG. We show that several GTP-binding proteins interact preferentially with 5'-pppG RNAs. Finally, supplementation with guanosine, but not adenosine, which rapidly increases intracellular concentrations of GTP and ATP, respectively, eliminates the difference in immunogenicity between 5'-pppG and 5'-pppA RNAs. Our findings suggest that 5'-pppG RNAs may enable certain RNA viruses and Pol III transcripts to limit detection by innate immune receptors. These results offer new insights into the sequence-dependent activation of the RIG-I/IFN pathway and have important implications for both antiviral immunity and the role of Pol III-derived RNAs in autoimmune diseases.

molecular biology↗

bioRxiv2022

Structure of human TRPM8 channel.

SUMMARYTRPM8 is a calcium ion channel that is activated by multiple factors, such as temperature, voltage, pressure, and osmolality. It is a therapeutic target for anticancer drug development, and its modulators can be utilized for several pathological conditions. Here, we present a cryo-electron microscopy structure of a human TRPM8 channel in the closed state that was solved at 2.7 [A] resolution. Based on our reconstruction, we built the most complete model of the N-terminal pre-melastatin homology region. We also visualized several ligands that are bound by the protein and modeled how the human channel interacts with icilin. Analyses of pore helices showed that all available TRPM8 structures can be grouped into closed and desensitized states based on the register of pore helix S6 and the resulting positioning of particular amino acid residues at the channel constriction.

molecular biology↗

bioRxiv2020

Morphology and immunhistchemical characteristics of the otic ganglion in chinchilla (Chinchila laniger Molina).

The available literature provides relatively little information on the morphology of the autonomic head ganglia in rodents including their neurochemical codding. The present study was thus designed to investigate the morphology and neurochemical properties of the otic ganglion in the chinchilla. The results will contribute to our knowledge of the organization of the autonomic nerve system in mammals. Morphological investigations of the otic ganglion were performed using the modified acetylcholinesterase method. The cellular structure was investigated with histological techniques and neurochemical properties were studied with double-labelling immunofluorescence method Macromorphological investigations allowed the otic ganglion to be identified as a compact, oval agglomeration of neurons and nerve fibers located inside the skull on the medial surface of the mandibular nerve, just above the oval foramen. Multidimensional cross-sections revealed densely arranged neuronal perikarya and two populations of nerve cells differing in size were distinguished. The large cells (40-50 m) accounted for about 80% of the neurons in the otic ganglion cross-sections. Moreover, a small number of intraganglionic nerve fibers was observed. Immunohistochemical staining revealed that over 85% of the neuronal cell bodies in the otic ganglion contained immunoreactivity to VAChT or ChAT. VIP-immunoreactive perikarya comprised approximately 10% of the ganglionic cells. Double staining revealed the presence of VAChT and NOS-positive neurons which amounted to about 45% of the nerve cells in the otic ganglion. NOS-positive only perikarya comprised approx. 15% of all the neurons. Immunoreactivity to enkephalin, substance P, somatostatin and galanin was expressed in single nerve cell bodies and nerve fibres except numerous SP-positive intraganglionic nerve fibres. Some of them stained also for CGRP. Single neurons stained for TH. The present results, compared with previous findings, suggest the existence interspecies differences in the morphology, cellular structure and immunohistochemical properties of the head autonomic ganglia in mammals.

neuroscience↗