Search Results (8)

Caviar yield, caviar color, and body weight are crucial economic traits in sturgeon breeding. Understanding the molecular mechanisms behind these traits is essential for their genetic improvement. In this study, we performed whole-genome sequencing on 673 Russian sturgeons, renowned for their high-quality caviar. With an average sequencing depth of 13.69×, we obtained approximately 10.41 million high-quality single nucleotide polymorphisms (SNPs). Using a genome-wide association study (GWAS) with a single-marker regression model, we identified SNPs and genes associated with these traits. Our findings revealed several candidate genes for each trait: caviar yield: TFAP2A, RPS6KA3, CRB3, TUBB, H2AFX, morc3, BAG1, RANBP2, PLA2G1B, and NYAP1; caviar color: NFX1, OTULIN, SRFBP1, PLEK, INHBA, and NARS; body weight: ACVR1, HTR4, fmnl2, INSIG2, GPD2, ACVR1C, TANC1, KCNH7, SLC16A13, XKR4, GALR2, RPL39, ACVR2A, ADCY10, and ZEB2. Additionally, using the genomic feature BLUP (GFBLUP) method, which combines linkage disequilibrium (LD) pruning markers with GWAS prior information, we improved genomic prediction accuracy by 2%, 1.9%, and 3.1% for caviar yield, caviar color, and body weight traits, respectively, compared to the GBLUP method. In conclusion, this study enhances our understanding of the genetic mechanisms underlying caviar yield, caviar color, and body weight traits in sturgeons, providing opportunities for genetic improvement of these traits through genomic selection. Full article

Formin Homology Proteins (Formins) are a highly conserved family of cytoskeletal regulatory proteins that participate in a diverse range of cellular processes. FMNL2 is a member of the Diaphanous-Related Formin sub-group, and previous reports suggest FMNL2’s role in filopodia assembly, force generation at lamellipodia, subcellular trafficking, cell–cell junction assembly, and focal adhesion formation. How FMNL2 is recruited to these sites of action is not well understood. To shed light on how FMNL2 activity is partitioned between subcellular locations, we used biotin proximity labeling and proteomic analysis to identify an FMNL2 interactome. The interactome identified known and new FMNL2 interacting proteins with functions related to previously described FMNL2 activities. In addition, our interactome predicts a novel connection between FMNL2 and extracellular vesicle assembly. We show directly that FMNL2 protein is present in exosomes. Full article

Background: Thromboangiitis obliterans (TAO) causes vascular insufficiency due to chronic inflammation and abrupt thrombosis of the medium and small arteries of the extremities. In our study, we aimed to determine biomarkers for the diagnosis of TAO by evaluating 15 male TAO patients with Shinoya diagnostic criteria and 5 healthy controls who did not have TAO-related symptoms in their family histories. Methods: The Clariom D Affymetrix platform was used to conduct microarray analysis on total RNA extracted from whole blood. A total of 477 genes (FC ≤ 5 or >5) common to the fifteen patient and five control samples were selected using comparative microarray analysis; among them, 79 genes were upregulated and 398 genes were downregulated. Results: According to FC ≤ 10 or >10, in the same TAO patient and control group, 13 genes out of 28 were upregulated, whereas 15 genes were downregulated. The 11 key genes identified according to their mean log2FC values were PLP2, RPL27A, CCL4, FMNL1, EGR1, EIF4A1, RPL9, LAMP2, RNF149, EIF4G2, and DGKZ. The genes were ranked according to their relative expression as follows: FMNL1 > RNF149 > RPL27A > EIF4G2 > EIF4A1 > LAMP2 > EGR1 > PLP2 > DGKZ > RPL9 > CCL4. Using protein–protein interaction network analysis, RPL9, RPL27A, and RPL32 were found to be closely related to EIF4G2 and EIF4A1. The Reactome pathway found pathways linked to 28 genes. These pathways included the immune system, cellular responses to stress, cytokine signaling in the immune system, and signaling by ROBO receptors. Conclusions: By figuring out the protein expression levels of the genes that have been found to explain how TAO disease works at the molecular level, it will be possible to figure out how well these chosen transcripts can diagnose and predict the disease. Full article

Glomerulonephritis are renal disorders resulting from different pathogenic mechanisms (i.e., autoimmunity, complement, inflammatory activation, etc.). Clarifying details of the pathogenic cascade is basic to limit the progression from starting inflammation to degenerative stages. The balance between tissue injury, activation of protective systems and renal tissue repair determines the final outcome. Induction of an oxidative stress is part of glomerular inflammation and activation of protective antioxidant systems has a crucial role in reducing tissue effects. The generation of highly reactive oxygen species can be evaluated in vivo by tracing the inner-layer content of phosphatidyl ethanolamine and phosphatidyl serine in cell membranes. Albumin is the major antioxidant in serum and the level of oxidized albumin is another indirect sign of oxidative stress. Studies performed in Gn, specifically in FSGS, showed a high degree of oxidation in most contexts. High levels of circulating anti-SOD2 antibodies, limiting the detoxyfing activity of SOD2, have been detected in autoimmune Gn(lupus nephritis and membranous nephropathy) in association with persistence of proteinuria and worsening of renal function. In renal transplant, high levels of circulating anti-Glutathione S-transferase antibodies have been correlated with chronic antibody rejection and progressive loss of renal function. Annexins, mainly ANXA1 and ANXA2, play a general anti-inflammatory effect by inhibiting neutrophil functions. Cytosolic ANXA1 is decreased in apoptotic neutrophils of patients with glomerular polyangitis in association with delayed apoptosis that is considered the mechanism for polyangitis. High circulating levels of anti-ANXA1 and anti-ANXA2 antibodies characterize lupus nephritis implying a reduced anti-inflammatory effect. High circulating levels of antibodies targeting Macrophages (anti-FMNL1) have been detected in Gn in association with proteinuria. They potentially modify the intra-glomerular presence of protective macrophages (M2a, M2c) thus acting on the composition of renal infiltrate and on tissue repair. Full article

The actin nucleating and polymerizing formin-like 2 (FMNL2) is upregulated in several cancers and has been shown to play important roles in cell migration, invasion, cell–cell adhesion and filopodia formation. Here, using structured illumination microscopy we show that FMNL2 promotes rapid and highly dynamic filopodia formation in epithelial cells while remaining on the tip of the growing filopodia. This filopodia tip localization depends fully on its N-terminal myristoylation. We further show that FMNL2-dependent filopodia formation requires its serine 1072 phosphorylation within the diaphanous-autoregulatory domain (DAD) by protein kinase C (PKC) α. Consistent with this, filopodia formation depends on PKC activity and PKCα localizes to the base of growing filopodia. Thus, a PKCα–FMNL2 signaling module spatiotemporally controls dynamic filopodia formation. Full article

Background: Filopodia are dynamic, finger-like actin-filament bundles that overcome membrane tension by forces generated through actin polymerization at their tips to allow extension of these structures a few microns beyond the cell periphery. Actin assembly of these protrusions is regulated by accessory proteins including heterodimeric capping protein (CP) or Ena/VASP actin polymerases to either terminate or promote filament growth. Accordingly, the depletion of CP in B16-F1 melanoma cells was previously shown to cause an explosive formation of filopodia. In Ena/VASP-deficient cells, CP depletion appeared to result in ruffling instead of inducing filopodia, implying that Ena/VASP proteins are absolutely essential for filopodia formation. However, this hypothesis was not yet experimentally confirmed. Methods: Here, we used B16-F1 cells and CRISPR/Cas9 technology to eliminate CP either alone or in combination with Ena/VASP or other factors residing at filopodia tips, followed by quantifications of filopodia length and number. Results: Unexpectedly, we find massive formations of filopodia even in the absence of CP and Ena/VASP proteins. Notably, combined inactivation of Ena/VASP, unconventional myosin-X and the formin FMNL3 was required to markedly impair filopodia formation in CP-deficient cells. Conclusions: Taken together, our results reveal that, besides Ena/VASP proteins, numerous other factors contribute to filopodia formation. Full article

Tumor cells can be recognized through tumor surface antigens by immune cells and antibodies, which therefore can be used as drug targets for chimeric antigen receptor-T (CAR-T) therapies and antibody drug conjugates (ADCs). In this study, we aimed to identify novel tumor-specific antigens as targets for more effective and safer CAR-T cell therapies and ADCs. Here, we performed differential expression analysis of pan-cancer data obtained from the Cancer Genome Atlas (TCGA), and then performed a series of conditional screenings including Cox regression analysis, Pearson correlation analysis, and risk-score calculation to find tumor-specific cell membrane genes. A tumor tissue-specific and highly expressed gene set containing 3919 genes from 17 cancer types was obtained. Moreover, the prognostic roles of these genes and the functions of these highly expressed membrane proteins were assessed. Notably, 427, 584, 431 and 578 genes were identified as risk factors for LIHC, KIRC, UCEC, and KIRP, respectively. Functional enrichment analysis indicated that these tumor-specific surface proteins might confer tumor cells the ability to invade and metastasize. Furthermore, correlation analysis displayed that most overexpressed membrane proteins were positively correlated to each other. In addition, 371 target membrane protein-coding genes were sifted out by excluding proteins expressed in normal tissues. Apart from the identification of well-validated genes such as GPC3, MSLN and EGFR in the literature, we further confirmed the differential protein expression of 23 proteins: ADD2, DEF6, DOK3, ENO2, FMNL1, MICALL2, PARVG, PSTPIP1, FERMT1, PLEK2, CD109, GNG4, MAPT, OSBPL3, PLXNA1, ROBO1, SLC16A3, SLC26A6, SRGAP2, and TMEM65 in four types of tumors. In summary, our findings reveal novel tumor-specific antigens, which could be potentially used for next-generation CAR-T cell therapies and ADC discovery. Full article

Glioblastoma multiforme (GBM), the most common primary malignant brain tumor in adults, is characterized by rapid proliferation, aggressive migration, and invasion into normal brain tissue. Formin proteins have been implicated in these processes. However, the role of formin-like 1 (FMNL1) in cancer remains unclear. We studied FMNL1 expression in glioblastoma samples using immunohistochemistry. We sought to analyze the correlation between FMNL1 expression, clinicopathologic variables, and patient survival. Migration and invasion assays were used to verify the effect of FMNL1 on glioblastoma cell lines. Microarray data were downloaded from The Cancer Genome Atlas and analyzed using gene set enrichment analysis (GSEA). FMNL1 was an independent predictor of poor prognosis in a cohort of 217 glioblastoma multiforme cases (p < 0.001). FMNL1 expression was significantly higher in the mesenchymal subtype. FMNL1 upregulation and downregulation were associated with mesenchymal and proneural markers in the GSEA, respectively. These data highlight the important role of FMNL1 in the neural-to-mesenchymal transition. Conversely, FMNL1 downregulation suppressed glioblastoma multiforme cell migration and invasion via DIAPH1 and GOLGA2, respectively. FMNL1 downregulation also suppressed actin fiber assembly, induced morphological changes, and diminished filamentous actin. FMNL1 is a promising therapeutic target and a useful biomarker for GBM progression. Full article