Biology subjects

Brelidze, T. I.

Publications and source records attributed to Brelidze, T. I..

3 recordsLinked to original sources

bioRxiv2024

VICR: A Novel Software for Unbiased Video and Image Analysis in Scientific Research

In scientific research, objectivity and unbiased data analysis is crucial for the validity and reproducibility of outcomes. This is particularly important for studies involving video or image categorization. A common approach of decreasing the bias is delegating data analysis to researchers unfamiliar with the experimental settings. However, this requires additional personnel and is prone to cognitive biases. Here we describe the Video & Image Cutter & Randomizer (VICR) software (https://github.com/kkihnphd/VICR), designed for unbiased analysis by segmenting and then randomizing videos or still images. VICR allows a single researcher to conduct and analyze studies in a blinded manner, eliminating the bias in analysis and streamlining the research process. We describe the features of the VICR software and demonstrate its capabilities using zebrafish behavior studies. To our knowledge, VICR is the only software for the randomization of video and image segments capable of eliminating bias in data analysis in a variety of research fields.

animal behavior and cognition↗

bioRxiv2023

gp120 envelope glycoproteins of HIV-1 Group M Subtype A and Subtype B differentially affect gene expression in human vascular endothelial cells

Cardiovascular complications are seen among human immunodeficiency virus (HIV)-positive individuals who can now survive longer due to successful antiretroviral therapies. Among them, pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased blood pressure in the lung circulation due to vasoconstriction and vascular wall remodeling, resulting in the overworking of the heart. The prevalence of PAH in the HIVpositive population is dramatically higher than that in the general population. While HIV-1 Group M Subtype B is the most prevalent subtype in western countries, the majority of HIV-1 infections in eastern Africa and former Soviet Union countries are caused by Subtype A. Research on the mechanism of vascular complications in the HIV-positive population, especially in the context of subtype differences, however, has not been rigorous. Much of the research on HIV has focused on Subtype B and information on the molecular mechanisms of Subtype A is non-existent. The lack of such knowledge results in health disparities in the development of therapeutic strategies to prevent/treat HIV complications. The present study examined the effects of HIV-1 viral fusion protein gp120 of Subtypes A and B on cultured human pulmonary artery endothelial cells by performing protein arrays. We found that the gene expression changes caused by the gp120s of Subtypes A and B are different. Specifically, Subtype A is a more potent downregulator of perostasin, matrix metalloproteinase-2 (MMP-2), and ErbB/Her3 than Subtype B, while Subtype B is more effective in downregulating monocyte chemotactic protein-2 (MCP-2/CCL8), MCP-3 (CCL7), and thymus- and activation-regulated chemokine (TARC/CCL17) proteins. This is the first report of gp120 proteins affecting host cells in an HIV subtype-specific manner, opening up the possibility that vascular complications may occur differently in HIV patients throughout the world.

cell biology↗

bioRxiv2020

HCN domain is required for HCN channel expression and couples voltage- and cAMP-dependent gating mechanisms

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are major regulators of synaptic plasticity, and rhythmic activity in the heart and brain. Opening of HCN channels requires membrane hyperpolarization and is further facilitated by intracellular cyclic nucleotides (cNMPs). In HCN channels, membrane hyperpolarization is sensed by the membrane-spanning voltage sensor domain (VSD) and the cNMP-dependent gating is mediated by the intracellular cyclic nucleotide-binding domain (CNBD) connected to the pore-forming S6 transmembrane domain via the C-linker. Previous functional analysis of HCN channels suggested a direct or allosteric coupling between the voltage- and cNMP-dependent activation mechanisms. However, the specifics of the coupling were unclear. The first cryo-EM structure of an HCN1 channel revealed that a novel structural element, dubbed HCN domain (HCND), forms a direct structural link between the VSD and C-linker/CNBD. In this study, we investigated the functional significance of the HCND. Deletion of the HCND prevented surface expression of HCN2 channels. Based on the HCN1 structure analysis, we identified R237 and G239 residues on the S2 of the VSD that form direct interactions with I135 on the HCND. Disrupting these interactions abolished HCN2 currents. We then identified three residues on the C-linker/CNBD (E478, Q382 and H559) that form direct interactions with residues R154 and S158 on the HCND. Disrupting these interactions affected both voltage- and cAMP-dependent gating of HCN2 channels. These findings indicate that the HCND is necessary for the surface expression of HCN channels, and provides a functional link between the voltage- and cAMP-dependent mechanisms of HCN channel gating.

biophysics↗