Search Results (208)

The cell wall integrity pathway is activated in response to cell wall stress (CWS). The defense system in aspergilli employs three transcription factors—RlmA, MsnA, and CrzA—which also facilitate adaptation to various abiotic stressors and involve alterations in cytosolic osmolyte composition and membrane lipid profiles. However, their role in adaptation to CWS remains unclear. In Aspergillus niger, CWS induced by Congo red and calcofluor white caused a pronounced cessation of apical growth, accompanied by hyphal globular swelling and an increase in chitin and glucan content in the cell wall. Regarding the osmolyte composition, which predominantly consists of low levels of glycerol and mannitol, glycerol levels were reduced under CWS. Neither the composition nor the amounts of membrane and storage lipids changed following CWS; however, the degree of unsaturation of phospholipids increased due to a higher proportion of linolenic acid, potentially enhancing membrane fluidity. These minor rearrangements of membrane lipids and osmolytes do not confirm their involvement in the adaptation to CWS induced by Congo red and calcofluor white, contrary to previous assumptions based on studies of cell wall integrity pathways. Full article

Microsomal fractions from yeast Δale1 cells harbouring the empty plasmid pYES2/CT and from yeast cells overexpressing PtATS2a (Phatr3_J11916) or PtATS2b (Phatr3_J43099) were used in the studies. When sn-1-18:1-LPA and [¹⁴C]16:0-CoA were used as exogenous substrates, both PtATS2a and PtATS2b showed the highest activity at 23 °C in the range of temperatures tested from 10 to 60 °C. Both enzymes showed the highest activity in alkaline pH. For PtATS2a, it was pH 10 while for PtATS2b, it was pH 11. At pH 6 and pH 12, the activities of both enzymes were very low. The calcium ions at concentrations of 0.05–1 mM drastically decreased the activity of both enzymes. The magnesium ions at a concentration of 0.05 mM had a little effect on the activity of both enzymes, while higher concentrations (0.5 mM and 1 mM) significantly inhibited their activity. To study the substrate specificity, seventeen different acyl-CoAs in combinations with sn-1-[¹⁴C]18:1-LPA were used. PtATS2a showed the highest preference for 18:4-CoA n-3 while PtATS2b for 18:1-CoA. The pattern of utilisation of other acyl-CoAs tested also differed between the two enzymes. The presented studies, for the first time, characterised LPAAT type enzymes from diatoms, organisms that naturally produced very-long-chain polyunsaturated fatty acids (VLC-PUFA). Full article

Sperm membrane lipids play a crucial role in male fertility, influencing sperm motility, viability, and functional competence. This study comprehensively characterizes the phospholipid and sphingolipid composition in highly motile human spermatozoa obtained through the swim-up method, a widely used technique in assisted reproductive technology (ART). Using two-dimensional thin-layer chromatography and phosphorus analysis, we identified choline glycerophospholipids (CGP, 45%), ethanolamine glycerophospholipids (EGP, 26%), and sphingomyelin (SM, 17%) as predominant phospholipids, with minor components including cardiolipin, lysophospholipids, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and neutral lipids. Gas chromatography analysis of glycerophospholipids (GPL) revealed a high long chain (C20–C22) polyunsaturated fatty acids (PUFA) content (46.3%), particularly docosahexaenoic acid (DHA, 22:6n-3), which was more abundant in CGP (46%) than EGP (26%). Sphingolipid analysis indicated that ceramide (Cer) and SM shared similar fatty acid profiles due to their metabolic relationship, with very-long-chain (VLC) PUFA (≥C26) being more prevalent in SM (10%) than in Cer (6%). Additionally, argentation chromatography identified highly unsaturated VLCPUFA species in Cer, including 28:3n-6, 28:4n-6, and 30:4n-6, which had not been previously quantified in motile human spermatozoa. Given the essential function of sphingolipid metabolism in spermatogenesis, capacitation, and acrosomal exocytosis, our findings suggest that the balance of VLCPUFA-containing SM and Cer could play a role in sperm performance and fertilization potential. This study provides novel insights into the lipid signature of human sperm and highlights the relevance of membrane lipid remodeling for male fertility and ART outcomes. Full article

Background: Obesity poses a significant threat to human health and is commonly caused by excessive dietary intake. Phosphatidic acid (PA) is one of the simplest diacylglycerol phospholipids, serving as a crucial precursor for the synthesis of triglycerides and other complex phospholipids. PA is also an important intermediate product in the process of fat digestion and absorption. Studies have shown that PA has muscle-building and fat-reducing effects, but it is currently unclear whether it can combat obesity induced by a high-fat, high-sugar diet (HFD). Methods: Using a model of obesity induced by a high-fat high-sugar diet, we found that the addition of PA to food could reverse HFD-induced obesity. Results: Addition of PA to food can reverse obesity induced by a high-fat diet. Transcriptomic analysis results indicate that this reversal also takes place at the molecular level. Further analysis suggests that PA may regulate fat metabolism by reversing the PPAR signaling pathway. Conclusions: Our study provides molecular evidence for the use of PA as an effective additive in weight-loss food products. Full article

This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated by surface spraying, with distilled water serving as the control. The effects of the coating on storage quality, physicochemical properties, reactive oxygen species (ROS) metabolism, and membrane lipid metabolism were evaluated during storage at (25 ± 1) °C. The results showed that the ε-PL/CTS composite coating significantly retarded quality deterioration, as evidenced by reduced weight loss, maintained whiteness and color, and higher retention of soluble sugars, soluble solids, and soluble proteins. The coating also effectively limited water migration and loss. Mechanistically, the coated T. fuciformis exhibited enhanced antioxidant capacity, characterized by increased superoxide anion (O₂⁻) resistance capacity, higher activities of antioxidant enzymes (SOD, CAT, APX), and elevated levels of non-enzymatic antioxidants (AsA, GSH). This led to a significant reduction in malondialdehyde (MDA) accumulation, alongside improved DPPH radical scavenging activity and reducing power. Furthermore, the ε-PL/CTS coating preserved cell membrane integrity by inhibiting the activities of lipid-degrading enzymes (lipase, LOX, PLD), maintaining higher levels of key phospholipids (phosphatidylinositol and phosphatidylcholine), delaying phosphatidic acid accumulation, and consequently reducing cell membrane permeability. In conclusion, the ε-PL/CTS composite coating effectively extends the shelf life and maintains the quality of postharvest T. fuciformis by modulating ROS metabolism and preserving membrane lipid homeostasis. This study provides a theoretical basis and a practical approach for the quality control of fresh T. fuciformis. Full article

Background: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. Methods: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) (n = 20). Tissue was collected from the endometrium of all 54 patients, including patients with HY, EC, and CO, who underwent total hysterectomy. EC and HY diagnoses were confirmed based on histological examination. Untargeted metabolomics profiling was conducted using LC-HRMS. The partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for univariate and multivariate statistical analysis. The fitness of the model (R2Y) and predictive ability (Q2) were used to create OPLS-DA models. ROC analysis was carried out, followed by network analysis using Ingenuity Pathway Analysis. Results: The top metabolites that can discriminate EC and HY from CO were identified. This revealed a decrease in the levels of the lipid species, specifically phosphatidic acid (PA) (PA (14:1/14:0), PA(10:0/17:0), PA(18:1-O(12,13)/12:0)), PG(a-13:0/a-13:0), ganglioside GA1 (d18:1/18:1), PS(14:1/14:0), TG(20:0/18:4/14:1), and CDP-DG(PGF2alpha/18:2), while the levels of 3-Dehydro-L-gulonate, Uridine diphosphate-N-acetylglucosamine, ganglioside GT2 (d18:1/14:0), gamma-glutamyl glutamic acid and oxidized glutathione were increased in cases of EC and HY as compared to CO. Bioinformatics analysis, specifically using Ingenuity Pathway Analysis (IPA), revealed distinct pathway enrichments for EC and HY. For EC, the most highly scored pathways were associated with cell-to-cell signaling and interaction, skeletal and muscular system development and function, and small-molecule biochemistry. In contrast, HY cases showed the highest scoring pathways related to inflammatory disease, inflammatory response, and organismal injury and abnormalities. Conclusions: Developing sensitive biomarkers could improve diagnosis and guide treatment decisions, particularly in identifying which patients with HY may safely avoid hysterectomy and be managed with hormonal therapy. Full article

PLA2G16 is a member of the phospholipase A2 family that catalyzes the generation of lysophosphatidic acids (LPAs) and free fatty acids (FFAs) from phosphatidic acid. Previously, PLA2G16 was found to be a host factor for picornaviruses. Here, we discovered that the Foot-and-Mouth Disease Virus (FMDV) infection led to an elevation in PLA2G16 transcription. We established PLA2G16 overexpression and knockdown cell lines in PK-15 cells to investigate the potential role of PLA2G16 in FMDV infection. Our findings revealed that during FMDV infection, PLA2G16-overexpressing cells had increased levels of phosphorylated STAT1 and the interferon-stimulating factors ISG15 and ISG56. In PLA2G16-overexpressing cells, p-STAT1 was observed at higher levels and earlier than in wild-type cells. Subsequent research demonstrated that PLA2G16 specifically promoted an antiviral innate immune response against FMDV. The host could detect the early release of FMDV viral nucleic acid in PLA2G16-overexpressing cells and trigger the interferon signaling pathway. Additionally, we discovered that the supernatants of PLA2G16-overexpressing cells stimulated the production of higher levels of ISG56 and phosphorylated STAT1. This suggests that PLA2G16-overexpressing cells can activate the innate immune pathway of uninfected cells after FMDV infection. Full article

1-Acylglycerol-3-phosphate O-acyltransferase (1-AGPAT) is an enzyme family composed of 11 isoforms. Notably, 1-AGPAT 2, the most studied isoform since its discovery, is a critical enzyme in the triglyceride synthesis pathway, converting lysophosphatidic acid to phosphatidic acid. In addition, AGPAT2 gene expression is shown to be essential for adipocyte development and maturation. Defects in AGPAT2 are responsible for significant pathophysiological alterations related to adipose tissue (AT). Pathogenic variants in this gene are the molecular etiology of Congenital Generalized Lipodystrophy type 1 (CGL1), in which fatty tissue is absent from birth. Metabolically, these individuals have several metabolic complications, including hypoleptinemia, hypoadiponectinemia, hyperglycemia, and hypertriglyceridemia. Furthermore, numerous AGPAT2 pathogenic variants that enormously affect the amino acid sequence, the tertiary structure of 1-AGPAT 2, and their transmembrane and functional domains were found in CGL1 patients. However, studies investigating the genotype–phenotype relationship in this disease are scarce. Here, we used bioinformatics tools to verify the effect of the main pathogenic variants reported in the AGPAT2 gene: c.366-588del, c.589-2A>G, c.646A>T, c.570C>A, c.369-372delGCTC, c.202C>T, c.514G>A, and c.144C>A in the 1-AGPAT 2 membrane topology. We also correlated the phenotype of CGL1 subjects harboring these variants to understand the genotype–phenotype relationship. We provided an integrative view of clinical, genetic, and metabolic features from CGL1 individuals, helping to understand the role of 1-AGPAT 2 in the pathogenesis of this rare disease. Data reviewed here highlight the importance of new molecular studies to improve our knowledge concerning clinical and genetic heterogeneity in CGL1. Full article

The sodium/proton exchanger NHA2, also known as SLC9B2, is important for insulin secretion, renal blood pressure regulation, and electrolyte retention. Recent structures of bison NHA2 has revealed its unique 14-transmembrane helix architecture, which is different from SLC9A/NHE members made up from 13-TM helices. Sodium/proton exchangers are functional homodimers, and the additional N-terminal helix in NHA2 was found to alter homodimer assembly. Here, we present the cryo-electron microscopy structures of apo human NHA2 in complex with a Fab fragment and also with the inhibitor phloretin bound at 2.8 and 2.9 Å resolution, respectively. We show how phosphatidic acid (PA) lipids bind to the homodimer interface of NHA2 on the extracellular side, which we propose has a regulatory role linked to cell volume regulation. The ion binding site of human NHA2 has a salt bridge interaction between the ion binding aspartate D278 and R432, an interaction previously broken in the bison NHA2 structure, and these differences suggest a possible ion coupling mechanism. Lastly, the human NHA2 structure in complex with phloretin offers a template for structure-guided drug design, potentially leading to the development of more selective and potent NHA2 inhibitors. Full article

Background: The use of antimicrobial peptides (AMPs) as biotechnological tools is an area of growing interest in the research that seeks to improve crop defense. SmAP_α1–21 and SmAP_γ27–44 were previously reported to inhibit Fusarium graminearum, permeabilize the plasma membrane and induce cytoplasmic disorganization. To exert its activity, SmAP_α1–21 initially enters through the basal and apical cells of F. graminearum conidia and then displays a general but non-homogeneous distribution in the cytoplasm of all conidial cells, in contrast. Methods: We analyzed, focusing on membrane interaction, the mode of action of SmAP_γ27–44, a peptide based on the γ-core of defensins DefSm2-D and DefSm3, and SmAP_α1–21, based on the α-core of DefSm2-D. Additionally, we compared the behavior of SmAP_α1–21 with that of SmAP3_α1–21 based on DefSm3 but with no activity against F. graminearum. Results: In this study, we showed that SmAP_γ27–44 enters the cells with discrete intracellular localization. Furthermore, both peptides disrupted the plasma membrane, but with different modes of action. When large unilamellar liposomes (LUVs) containing phosphatidic acid and ergosterol were used as a filamentous fungal plasma membrane model, SmAP_γ27–44 strongly induced aggregation concomitantly with the solubilization of the liposomes and showed the maximal insertion of its tryptophan moiety into the membrane’s hydrophobic interior. In comparison, SmAP_α1–21 showed a high effect on the ζ potential of anionic vesicles, vesicle aggregation capacity after reaching a concentration threshold, and moderate transfer of tryptophan to the membrane. SmAP3_α1–21, on the other hand, showed poor superficial adsorption to liposomes. Conclusions: In view of our results, a cell penetration peptide-like effect was pictured for the γ-core defensin-derived peptide and a classical AMP action was observed for the α-core defensin-derived one. Full article

Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the transition period is only partially understood. Methods: Using a combination of reversed-phase liquid chromatography-mass spectrometry (RP-LC-MS), hydrophilic interaction-mass spectrometry (HILIC-MS), and lipid annotation software, we performed a comprehensive identification and quantification of serum of dairy cows in pasture-based Holstein-Friesian cows. The lipid remodelling induced by negative energy balance was investigated by comparing the levels of all identified lipids between the fresh lactation (5–14 days in milk, DIM) and full lactation (65–80 DIM) stages. Results: We identified 535 lipid molecular species belonging to 19 classes. The most abundant lipid class was cholesteryl ester (CE), followed by phosphatidylcholine (PC), sphingomyelin (SM), and free fatty acid (FFA), whereas the least abundant lipids included phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), acylcarnitine (AcylCar), ceramide (Cer), glucosylceramide (GluCer), and lactosylceramide (LacCer). Conclusions: A remarkable increase in most lipids and a dramatic decrease in FFAs, AcylCar, and DHA-containing species were observed at the full lactation compared to fresh lactation stage. Several serum lipid biomarkers for detecting negative energy balance in cows were also identified. Full article

Growing neurochemical evidence highlights cerebral lipid dysregulation as a key factor in the pathophysiology of major depressive disorder (MDD). This review systematically explores the dual roles of lipid species in both normal behavioral regulation and MDD development. By critically examining the recent literature, we classify these lipid species into two functional categories based on their functional neuroactivity: (1) neuroprotective lipids (sphingomyelin, cholesterol, cardiolipin, sphingosine, phosphatidic acid, and phosphatidylserine), which exert neuroprotective effects by modulating membrane fluidity and supporting synaptic vesicle trafficking; and (2) neurotoxic lipids (ceramides, phosphatidylinositol, phosphocholine, and phosphatidylethanolamine), which promote apoptotic signaling cascades and disrupt mitochondrial bioenergetics. An unresolved but critical question pertains to the maintenance of homeostatic equilibrium between these opposing lipid classes. This balance is essential, given their significant impact on membrane protein localization and function, monoaminergic neurotransmitter metabolism, energy homeostasis, and redox balance in neural circuits involved in mood regulation. This emerging framework positions cerebral lipidomics as a promising avenue for identifying novel therapeutic targets and developing biomarker-based diagnostic approaches for MDD treatment. Full article

A Gram-negative aerobic, motile bacterium KMM 10153^T was isolated from bottom sediment sampled from the Sea of Japan at a depth of 256 m, Russia. Strain KMM 10153^T grew in 0–12% NaCl at temperatures ranging from 4 to 42 °C and produced brown diffusible pigments. Based on the 16S rRNA gene and whole genome sequences analyses, novel bacterium KMM 10153^T was affiliated with the genus Oceanisphaera (phylum Pseudomonadota) showing the highest 16S rRNA gene sequence similarities of 98.94% to Oceanisphaera arctica KCTC 23013^T, 98.15% to Oceanisphaera donghaensis BL1^T, and similarity values of <98% to other validly described Oceanisphaera species. The pairwise Average Nucleotide Identity (ANI) and Average Amino Acid Identity (AAI) values between the novel strain KMM 10153^T and the three closest type strains Oceanishaera arctica KCTC 23013^T, Oceanisphaera litoralis DSM 15406^T and Oceanisphaera sediminis JCM 17329^T were 89.4%, 89.1%, 87.41%, and 90.7%, 89.8%, 89.7%, respectively. The values of digital DNA–DNA hybridization (dDDH) were below 39.3%. The size of the KMM 10153^T draft genome was 3,558,569 bp, and the GC content was 57.5%. The genome of KMM 10153^T harbors 343 unique genes with the most abundant functional classes consisting of transcription, mobilome, amino acid metabolism, and transport. Strain KMM 10153^T contained Q-8 as the predominant ubiquinone and C_16:1ω7c, C_16:0, and C_18:1ω7c as the major fatty acids. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and phosphatidic acid. Based on the distinctive phenotypic characteristics and the results of phylogenetic and genomic analyses, the marine bacterium KMM 10153^T could be classified as a novel Oceanisphaera submarina sp. nov. The type strain of the species is strain KMM 10153^T (=KCTC 8836^T). Full article

Phallus impudicus is a fungus used as a medicine and nutrient-rich food. However, the shelf life of mature Phallus impudicus is only a few hours. Therefore, research on its preservation technology is essential for improving its economic value. This study investigated the effects of hexanal concentrations (25–100 μL/L) and treatment time (4–8 h) on the inhibition of peach-shaped Phallus impudicus (CK) maturation and found that the maturation rate was 25% under optimal conditions of 25 μL/L hexanal treatment for 6 h. Quantitative transcriptomic and lipidomic analyses were conducted among CK, mature Phallus impudicus (M-P), and hexanal-treated peach-shaped Phallus impudicus (H-P-P). In total, 2933 and 2746 differentially expressed genes (DEGs) and 156 and 111 differentially abundant lipids (DALs) were identified in CK vs. H-P-P and M-P vs. H-P-P, respectively. Functional analysis demonstrated that hexanal treatment inhibited phospholipase D gene expression and reduced phosphatidic acid abundance, thereby inhibiting the activation of the phosphatidylinositol signaling system and the signal amplification of the cell wall integrity mitogen-activated protein kinase pathway. These blocked signal transductions inhibited the gene expression of most β-glucanases, chitinases and chitin synthases, further affecting cell wall reconstruction. Moreover, hexanal treatment enhanced membrane stability by reducing the monogalactosyl diglyceride/digalactosyl diacylglycerol ratio and increasing the phosphatidylcholine/phosphatidylethanolamine ratio. This study contributed to the development of hexanal treatment as a postharvest preservation technology for Phallus impudicus. Full article

Extrachromosomal circular DNAs (eccDNAs) has been found to be widespread and functional in various organisms. However, comparative analyses of pre- and post-infection of virus are rarely known. Herein, we investigated the changes in expression patterns of eccDNA following infection with Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) and explore the role of eccDNA in viral infection. Circle-seq was used to analyze eccDNAs in the midgut of BmCPV-infected and BmCPV-uninfected silkworms. A total of 5508 eccDNAs were identified, with sizes varying from 72 bp to 17 kb. Most of eccDNAs are between 100 to 1000 bp in size. EccDNA abundance in BmCPV-infected silkworms was significantly higher than in BmCPV-uninfected silkworms. GO and KEGG analysis of genes carried by eccDNAs reveals that most are involved in microtubule motor activity, phosphatidic acid binding, cAMP signaling pathway, and pancreatic secretion signaling pathways. Several eccDNAs contain sequences of the transcription factor SOX6, sem-2, sp8b, or Foxa2. Association analysis of eccDNA-mRNA/miRNA/circRNA revealed that some highly expressed genes are transcribed from relevant sequences of eccDNA and the transcription of protein coding genes influenced the frequency of eccDNA. BmCPV infection resulted in changes in the expression levels of six miRNAs, but no known miRNAs with altered expression levels due to changes in eccDNA abundance were identified. Moreover, it was found that 1287 and 924 sequences representing back-spliced junctions of circRNAs were shared by the junctions of eccDNAs in the BmCPV-infected and uninfected silkworms, respectively, and some eccDNAs loci were shared by circRNAs on Chromosomes 2, 7, 11, 14, and 24, suggesting some eccDNAs may exert its function by being transcribed into circRNAs. These findings suggest that BmCPV infection alter the expression pattern of eccDNAs, leading to changes in RNA transcription levels, which may play roles in regulating BmCPV replication. In the future, further experiments are needed to verify the association between eccDNA-mRNA/miRNA/circRNA and its function in BmCPV infection. Full article