Biomolecular Concepts最新文献

Wheat leaf rust, caused by fungal pathogen Puccinia triticina Erikss, annually contributes to production losses as high as 40% in susceptible varieties and remains as one of the most damaging diseases of wheat worldwide. Currently, one of the major challenges of wheat geneticists and breeders is to accumulate major genes for durability of rust resistance called "slow rusting" genes using marker-assisted selection (MAS). Until now, eight genes (Lr34/Yr18, Lr46/Yr29, Lr67/Yr46, Lr68, Lr74, Lr75, Lr77, and Lr78) conferring resistance against multiple fungal pathogens have been identified in wheat gene pool and the molecular markers were developed for them. In MAS practice, it is a common problem that cultivars exhibiting desirable marker genotypes may not necessarily have the targeted genes or alleles and vice versa, which is known as "false positives." The aim of this study was to compare the available four markers: Xwmc44, Xgwm259, Xbarc80, and csLV46G22 markers (not published yet), for the identification of the Lr46/Yr29 loci in 73 genotypes of wheat, which were reported as sources of various "slow rusting" genes, including 60 with confirmed Lr46/Yr29 gene, reported in the literature. This research revealed that csLV46G22 together with Xwmc44 is most suitable for the identification of resistance allele of the Lr46/Yr29 gene; however, there is a need to clone the Lr46/Yr29 loci to identify and verify the allelic variation of the gene and the function.

Systemic sclerosis (SSc) is an immune disorder characterized by diffuse fibrosis and vascular abnormalities of the affected organs. Although the etiopathology of this disease is largely unknown, endothelial damage and oxidative stress appear implicated in its initiation and maintenance. Here, we show for the first time that circulating factors present in SSc sera increased reactive oxygen species (ROS) production, collagen synthesis, and proliferation of human pulmonary microvascular endothelial cells (HPMECs). The observed phenomena were also associated with endothelial to mesenchymal transition (EndMT) as indicated by decreased von Willebrand factor (vWF) expression and increased alpha-smooth muscle actin, respectively, an endothelial and mesenchymal marker. SSc-induced fibroproliferative effects were prevented by HPMECs exposition to the NADPH oxidase inhibitor diphenyleneiodonium, demonstrating ROS's causative role and suggesting their cellular origin. Sera from SSc patients showed significant changes in the expression of a set of fibrosis/EndMT-associated microRNAs (miRNA), including miR-21, miR-92a, miR-24, miR-27b, miR-125b, miR-29c, and miR-181b, which resulted significantly upregulated as compared to healthy donors sera. However, miR29b resulted downregulated in SSc sera, whereas no significant differences were found in the expression of miR-29a in the two experimental groups of samples. Taking together our data indicate NADPH oxidase-induced EndMT as a potential mechanism of SSc-associated fibrosis, suggesting fibrosis-associated miRNAs as potentially responsible for initiating and sustaining the vascular alterations observed in this pathological condition.

Telomeres are protective caps at the end of eukaryotic chromosomes, whose length is correlated with health and lifespan. Telomere attrition is a common feature of the aging process and can be accelerated by oxidative stress and chronic inflammation. Various nutrients influence the telomere length, partially due to their antioxidant and anti-inflammatory properties. The aim of this review was to meta-analytically assess the effect of omega-3 fatty acids on the telomere length. We searched four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) from inception until November 2021. Of 573 records, a total of 5 clinical trials were included for the quantitative meta-analysis, comprising a total of 337 participants. The results revealed an overall beneficial effect of omega-3 fatty acids on the telomere length (mean difference = 0.16; 95% CI, 0.02, 0.30; p = 0.02). Despite a limited number of studies, the available evidence suggests that omega-3 fatty acids may positively affect the telomere length. However, larger clinical trials are needed to confirm our findings, along with studies aimed to clarify the underlying molecular mechanisms.

Atherosclerosis is an important medical and social problem, and the keys to solving this problem are still largely unknown. A common situation in real clinical practice is the comorbid course of atherosclerosis with chronic obstructive pulmonary disease (COPD). Diseases share some common risk factors and may be closely linked pathogenetically.

Methods: Bioinformatics analysis of datasets from Gene Expression Omnibus (GEO) was performed to examine the gene ontology (GO) of common differentially expressed genes (DEGs) in COPD and peripheral arterial atherosclerosis. DEGs were identified using the limma R package with the settings p < 0.05, corrected using the Benjamini & Hochberg algorithm and ǀlog 2FCǀ > 1.0. The GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and the protein-protein interaction (PPI) network analysis were performed with the detected DEGs.

Results: The biological processes and signaling pathways involving common DEGs from airway epithelial datasets in COPD and tissue in peripheral atherosclerosis were identified. A total of 15 DEGs were identified, comprising 12 upregulated and 3 downregulated DEGs. The GO enrichment analysis demonstrated that the upregulated hub genes were mainly involved in the inflammatory response, reactive oxygen species metabolic process, cell adhesion, lipid metabolic process, regulation of angiogenesis, icosanoid biosynthetic process, and cellular response to a chemical stimulus. The KEGG pathway enrichment analysis demonstrated that the common pathways were Toll-like receptor signaling pathway, NF-kappa B signaling pathway, lipid and atherosclerosis, and cytokine-cytokine receptor interaction.

Conclusions: Biological processes and signaling pathways associated with the immune response may link the development and progression of COPD and atherosclerosis.

Accurate prediction of protein structure is one of the most challenging goals of biology. The most recent achievement is AlphaFold, a machine learning method that has claimed to have solved the structure of almost all human proteins. This technological breakthrough has been compared to the sequencing of the human genome. However, this triumphal statement should be treated with caution, as we identified serious flaws in some AlphaFold models. Disordered regions are often represented by large loops that clash with the overall protein geometry, leading to unrealistic structures, especially for membrane proteins. In fact, AlphaFold comes up against the notion that protein folding is not solely determined by genomic information. We suggest that all parameters controlling the structure of a protein without being strictly encoded in its amino acid sequence should be coined "epigenetic dimension of protein structure." Such parameters include for instance protein solvation by membrane lipids, or the structuration of disordered proteins upon ligand binding, but exclude sequence-encoded sites of post-translational modifications such as glycosylation. In our view, this paradigm is necessary to reconcile two opposite properties of living systems: beyond rigorous biological coding, evolution has given way to a certain level of uncertainty and anarchy.