Lamins Organize the Global Three-Dimensional Genome from the Nuclear Periphery.

Lamins are structural components of the nuclear lamina (NL) that regulate genome organization and gene expression, but the mechanism remains unclear. Using Hi-C, we show that lamins maintain proper interactions among the topologically associated chromatin domains (TADs) but not their overall architecture. Combining Hi-C with fluorescence in situ hybridization (FISH) and analyses of lamina-associated domains (LADs), we reveal that lamin loss causes expansion or detachment of specific LADs in mouse ESCs. The detached LADs disrupt 3D interactions of both LADs and interior chromatin. 4C and epigenome analyses further demonstrate that lamins maintain the active and repressive chromatin domains among different TADs. By combining these studies with transcriptome analyses, we found a significant correlation between transcription changes and the interaction changes of active and inactive chromatin domains These findings provide a foundation to further study how the nuclear periphery impacts genome organization and transcription in development and NL-associated diseases.

The Interplay between Oxidative Stress and the Nuclear Lamina Contributes to Laminopathies and Age-Related Diseases.

Oxidative stress is a physiological condition that arises when there is an imbalance between the production of reactive oxygen species (ROS) and the ability of cells to neutralize them. ROS can damage cellular macromolecules, including lipids, proteins, and DNA, leading to cellular senescence and physiological aging. The nuclear lamina (NL) is a meshwork of intermediate filaments that provides structural support to the nucleus and plays crucial roles in various nuclear functions, such as DNA replication and transcription. Emerging evidence suggests that oxidative stress disrupts the integrity and function of the NL, leading to dysregulation of gene expression, DNA damage, and cellular senescence. This review highlights the current understanding of the interplay between oxidative stress and the NL, along with its implications for human health. Specifically, elucidation of the mechanisms underlying the interplay between oxidative stress and the NL is essential for the development of effective treatments for laminopathies and age-related diseases.

Immunoinformatics Identification of the Conserved and Cross-Reactive T-Cell Epitopes of SARS-CoV-2 with Human Common Cold Coronaviruses, SARS-CoV, MERS-CoV and Live Attenuated Vaccines Presented by HLA Alleles of Indonesian Population.

Reports on T-cell cross-reactivity against SARS-CoV-2 epitopes in unexposed individuals have been linked with prior exposure to the human common cold coronaviruses (HCCCs). Several studies suggested that cross-reactive T-cells response to live attenuated vaccines (LAVs) such as BCG (Bacillus Calmette-Guérin), OPV (Oral Polio Vaccine), and MMR (measles, mumps, and rubella) can limit the development and severity of COVID-19. This study aims to identify potential cross-reactivity between SARS-CoV-2, HCCCs, and LAVs in the context of T-cell epitopes peptides presented by HLA (Human Leukocyte Antigen) alleles of the Indonesian population. SARS-CoV-2 derived T-cell epitopes were predicted using immunoinformatics tools and assessed for their conservancy, variability, and population coverage. Two fully conserved epitopes with 100% similarity and nine heterologous epitopes with identical T-cell receptor (TCR) contact residues were identified from the ORF1ab fragment of SARS-CoV-2 and all HCCCs. Cross-reactive epitopes from various proteins of SARS-CoV-2 and LAVs were also identified (15 epitopes from BCG, 7 epitopes from MMR, but none from OPV). A majority of the identified epitopes were observed to belong to ORF1ab, further suggesting the vital role of ORF1ab in the coronaviruses family and suggesting it as a candidate for a potential universal coronavirus vaccine that protects against severe disease by inducing cell mediated immunity.

Role of the Nuclear Lamina in Age-Associated Nuclear Reorganization and Inflammation.

Aging is characterized by the gradual loss of tissue function and integrity. Activation of inflammatory responses accelerates the deterioration of cells and tissues. Many studies have shown that alteration of the components of the nuclear lamina is associated with inflammation, both in vivo and in vitro. However, the mechanism by which the nuclear lamina regulates inflammation is largely unknown. Recent studies have suggested that the nuclear lamina regulates both organization of the three-dimensional chromatin structure at the nuclear periphery and global gene expression, such as the expression of inflammatory response genes. Here, we discuss the current updates in the research on nuclear lamina alteration, activation of inflammation, and nuclear reorganization in models of cellular senescence and organismal aging.

Characterization of Proteus vulgaris K80 lipase immobilized on amine-terminated magnetic microparticles.

Proteus vulgaris K80 lipase was expressed in Escherichia coli BL21 (DE3) cells and immobilized on amine-terminated magnetic microparticles (Mag-MPs). The immobilization yield and activity retention were 84.15% and 7.87%, respectively. A homology model of lipase K80 was constructed using P. mirabilis lipase as the template. Many lysine residues were located on the protein surface, remote from active sites. The biochemical characteristics of immobilized lipase K80 were compared with the soluble free form of lipase K80. The optimum temperature of K80-Mag-MPs was 60°C, which was 20°C higher than that of the soluble form. K80-Mag-MPs also tended to be more stable than the soluble form at elevated temperatures and a broad range of pH. K80-Mag-MP maintained its stable form at up to 40°C and in a pH range of 5.0- 10.0, whereas soluble K80 maintained its activity up to 35°C and pH 6.0-10.0. K80-Mag-MPs had broader substrate specificity compared with that of soluble K80. K80-Mag-MPs showed about 80% residual relative activity after five recovery trials. These results indicate the potential benefit of K80-Mag-MPs as a biocatalyst in various industries.