Search Results (56)

Obesity causes lifestyle-related diseases such as hypertension and type 2 diabetes and has become a global health concern. L-fucose (Fuc), a monosaccharide that can be derived from brown algae, has been shown to strongly suppress lipid droplet accumulation in 3T3-L1 murine adipocytes at high concentrations via the activation of AMP-activated kinase (AMPK). Although low concentrations of Fuc also exhibited similar effects, the underlying mechanisms remain unclear. In this study, we investigated the effects of low-level Fuc on lipid metabolism, focusing on the role of fucosylation. Low-level Fuc did not induce AMPK phosphorylation but suppressed lipid droplet accumulation. This suppressive effect was abolished by co-treatment with the fucosylation inhibitor 2F-Peracetyl-Fucose (2F-PAF), suggesting that fucosylation plays a key role in the observed metabolic regulation. Furthermore, proteomic analysis combined with click chemistry pulldown suggested that proteins involved in the regulation of lipid metabolism, such as acetoacetyl-CoA synthetase enzymes and catalytic subunit alpha of cAMP-dependent protein kinase, are fucosylated or interact with fucose. These findings provide novel insights into the anti-obesity mechanisms of Fuc and highlight the physiological significance of protein fucosylation in adipocyte lipid metabolism. Full article

Platelet-activating factor (PAF) is a potent inflammatory mediator that activates the PAF receptor, which induces additional PAF production. Animal studies have shown that PAF induces inflammatory and neuropathic pain, including dysesthesia, a prodromal symptom of neuropathic pain. However, in humans, the association between PAF and pain remains unknown. Phospholipase A2 Group VII (PLA2G7) hydrolyzes PAF to eliminate PAF activity. The present study investigated the association between the PLA2G7 rs1051931 nonsynonymous polymorphism (T/C, Val379Ala), which decreases the PAF-degrading activity of PLA2G7 in plasma, and postoperative pain-related phenotypes in humans. The study included 303 patients who underwent sagittal split ramus osteotomy at Tokyo Dental College and were assessed for dysesthesia and 332 patients who underwent laparoscopic gynecologic surgery at Juntendo University Hospital and were assessed for postoperative pain using the Numeric Rating Scale (NRS). PLA2G7 rs1051931 was significantly associated with dysesthesia (p = 0.0491) and NRS scores (p = 0.0243). Carriers of the CC genotype of PLA2G7 rs1051931 were more likely to have dysesthesia and higher NRS scores than carriers of the TT + TC genotypes. Carriers of the CC genotype of PLA2G7 rs1051931 reportedly had lower PAF-degrading activity in plasma, thereby increasing the amount of PAF. The increase in PAF possibly leads to dysesthesia and postoperative pain in humans. Full article

The article presents the use of ground power sources for aircraft ground support. Both military and civil aircraft (A/C) require high-performance and reliable Ground Power Units (GPUs) to ensure safe operation in diverse environmental conditions. The power quality provided by these GPUs plays a crucial role in determining the reliability, cost efficiency and operational safety of the aircraft. The main objective of the article is to signal and propose a solution to the problems associated with the operation of GPUs in the Polish Armed Forces (PAF), resulting from the diversity of the equipment used (type, duration of operation, defects occurrence, etc.). Currently, the PAF utilize various types of GPUs to provide electrical power to aircraft while they are on the ground. Many of those devices have already been in service for many years. The presented statistics of defects registered in the airworthiness management system showed several dozen A/C failures or defects related to the operation of GPU. The authors highlight the importance and feasibility of diagnosing these ground-based power sources. The presented sample test results confirm that, following the methodology outlined in the article, it is possible to conduct comprehensive diagnostic assessment of the GPU systems currently in use by the PAF, as well as evaluate the quality of the electrical power they deliver in both steady and transient states. Full article

High-sensitivity and large-scale surveys are essential in advancing radio astronomy, enabling detailed exploration of the universe. A Phased Array Feed (PAF) installed in the focal plane of a radio telescope significantly enhances mapping efficiency by increasing the instantaneous Field of View (FoV) and improving sky sampling capabilities. This paper presents the design and optimization of a novel C-Band Phased Array Feed antenna for the Sardinia Radio Telescope (SRT). The system features an 8 × 8 array of dual-polarized elements optimized to achieve a uniform beam pattern and an edge taper of approximately 5 dB for single radiating elements within the 3.0–7.7 GHz frequency range. The proposed antenna addresses key efficiency limitations identified in the PHAROS 2 (PHased Arrays for Reflector Observing Systems) system, including the under-illumination of the Sardinia Radio Telescope’s primary mirror caused by narrow sub-array radiation patterns. By expanding the operational bandwidth and refining the radiation characteristics, this new design enables significantly improved performance across the broader frequency range of 3.0–7.7 GHz, enhancing the telescope’s capability for wide-field, high-resolution observations. Full article

The antioxidant, antithrombotic and anti-inflammatory effects of the amphiphilic compounds extracted from both avocado juice and by-products, were evaluated. All extracts were assessed for their total phenolic content (TPC) and total carotenoid content (TCC), and for their antioxidant activities by DPPH, ABTS and FRAP assays as well as for their anti-inflammatory and antithrombotic potency in human platelets. The extracts rich in TAC (Total Amphiphilic Content) showed much higher content in phenolics and carotenoids from the extracts of total lipophilic content (TLC), which was reflected by the much stronger antioxidant capacities of TAC extracts. ATR-FTIR spectroscopy revealed the presence of not only phenolics and carotenoids, but also of bioactive polar lipids (PLs) in avocado TAC extracts, the LC-MS based structural analysis of which further revealed a fatty acid composition favourable for unsaturated fatty acids (UFAs) versus saturated ones (SFAs), including monounsaturated fatty acids (MUFAs) like the oleic acid (C18:1n9) and omega-3 (n3) polyunsaturated fatty acids (PUFAs) like the alpha linolenic acid (C18:3n3), with the subsequent anti-inflammatory low values of the n6/n3 PUFA ratio. The presence of such bioactive PLs that are rich in UFA within the TAC extracts of avocado juice and its by-products provide an explanation for the observed potent anti-inflammatory and antithrombotic activities of avocado TAC against thrombo-inflammatory mediators like platelet activating factor (PAF) and against standard platelet agonists like ADP, offering promise for such avocado TAC extracts, as ingredients in functional products for health/promoting applications either in cosmetics or in functional foods and nutraceuticals, or even drugs. Full article

Background: Eukaryotic RNA polymerase I consists of 12 or 11 core subunits and three dissociable subunits, Rrn3, A34, and A49. The A34 and A49 subunits exist as a heterodimer. In silico analysis of the A34 family of transcription factors demonstrates a commonly shared domain structure despite a lack of sequence conservation, as well as N–terminal and C-terminal disordered regions. The common structure of A34 has an N–terminal disordered region followed by a dimerization domain that, in conjunction with A49, contributes to a fold that resembles the TFIIF core. This in turn is followed by a short region that cryo-EM demonstrates resembles an arm and intimately interacts with the PolR1A, PolR1B, and PolR1C subunits of Pol I. Analyses: This Pol I–binding domain is then followed by a region that is not resolved in cryo-EM and is predicted to be intrinsically disordered. Interestingly, the size/length of this disordered structure increases from yeast to humans, and is composed of repeats with unique sequence and biochemical features that also increase in number. Further analyses of the A34 CTD (carboxy–terminal domain) indicate that it has a high probability of undergoing liquid–liquid phase separation. Conclusions: We suggest that this intrinsically disordered domain found in the A34 family of Pol I transcription factors serves a function similar to the CTD of the PolR2A subunit in coordinating transcription initiation and elongation and RNA processing. Lastly, we propose that dynamic acetylation of PAF49 may regulate interactions of the intrinsically disordered CTD and thereby specify liquid–liquid phase separations. Overall, we propose a new paradigm for a repeat-containing CTD in Pol I transcription. Full article

Background/Objectives: Marine organisms, including shrimps, have gained research interest due to containing an abundance of bioactive lipid molecules.This study evaluated the composition and the in vitro biological activities of amphiphilic bioactive compounds from four different wild shrimp species: Litopenaeus vannamei, Penaeus kerathurus, Aristaeomorpha foliacea, and Parapenaeus longirostris. Methods: Total lipid (TL) extracts were obtained from shrimp and separated into total amphiphilic (TAC) and total lipophilic (TLC) compounds. Phenolic (TPC) and carotenoid (TCC) contents, antioxidant activities (DPPH, ABTS, FRAP assays), and biological effects on platelet-activating factor (PAF) and ADP-induced platelet activation were evaluated. Structural analyses were performed using ATR-FTIR spectroscopy, while LC-MS was used to elucidate the fatty acid composition and overall structure of polar lipids (PLs) present in shrimp TAC extracts. Results: TAC extracts, rich in phenolics, carotenoids, PL, and unsaturated fatty acids (UFAs), exhibited stronger anti-inflammatory and antithrombotic activities compared with TLC extracts, which showed potent antioxidant capacity. Significant amounts of UFAs, such as the monounsaturated fatty acid (MUFA) oleic acid (C18:1n9) and omega-3 (n3) polyunsaturated fatty acids (PUFAs) like eicosapentaenoic acid (EPA; C20:5n3) and docosahexaenoic acid (DHA; C22:6n3), were detected in the PLs of shrimp TAC extracts, with favorable anti-inflammatory values for their n6/n3 PUFA ratio. Shrimp amphiphilic bioactives present in the TAC extracts provide anti-inflammatory effects against the PAF pathway and antithrombotic effects against ADP and eicosanoid pathways. Conclusions: The overall findings support further study on the use of shrimp extracts rich in anti-inflammatory, anti-thrombotic, and antioxidant amphiphilic bioactives as ingredients to produce new bio-functional health-promoting products, in the context of sustainable development and circular economy. Full article

Platelet-activating factor (PAF) is a potent lipid mediator, involved in thrombosis, inflammation, and atherosclerosis. The protective effect of wine and olive oil against atherosclerotic diseases is largely attributed to their phenolic compounds and mostly to resveratrol and tyrosol. Both compounds have been reported to inhibit PAF biosynthesis in interleukin-1β (IL-1β)-stimulated monocytes and also to attenuate PAF biosynthesis in cell lysates. The aim of this study was to investigate the effects of resveratrol, tyrosol, and their derivatives on unstimulated U937 cells and to explore the intracellular messaging pathways that participate in the activation of PAF biosynthesis in the same cell line. Tyrosol and its derivatives did not exert any substantial effect on PAF biosynthesis. Resveratrol (50 and 100 μM), as well as its methoxy derivative (5–20 μM), caused a reduction in the PAF biosynthetic enzymes’ activity by 20–43% after 24 h of incubation. On the other hand, lower resveratrol concentration (10 μM) and higher concentration of the methoxy derivative (50 μM) increased the Ca²⁺-dependent lyso–PAF acetyltransferase (LysoPAF-ATC) activity by 28–45% after half-hour incubation via p38 mitogen-activated protein kinase (p38-MAPK) action. IL-1β activated PAF biosynthetic pathways via different signaling pathways, with phospholipase C-β (PLC-β) being a key enzyme. Full article

Ginkgo biloba extract (EGB) has been approved by the Food and Drug Administration in the United States for clinical studies on memory disorders. Ginkgolide B (GB) is the major terpene lactone component of EGB and is a specific and potent antagonist of platelet-activating factor (PAF). In a previous study, we reported the medium composition for the conversion of ginkgolides to GB by Coprinus comatus. In the present study, we applied the response surface methodology (RSM) to optimize the conversion conditions in a 20 L fermenter and applied HPLC-MS/MS, circular dichroism (CD) and infrared (IR) spectroscopy analyses, and nuclear magnetic resonance (NMR) to further confirm the sample structure. The optimal conversion conditions consisted of 12.7 L/min of ventilation, a 156 h conversion time, a 132 rpm rotating speed, a 0.04 MPa fermenter pressure, and a 27.8 °C conversion temperature. Under the optimal conditions, the GB conversion rate was 98.62%, and the GB content of the sample was higher than 98%. HPLC-MS/MS, CD, IR, and NMR analyses showed that the molecular formula of the sample was C₂₀H₂₄O₁₀ and the chemical structure of the sample was in good agreement with the standard GB. Our current study lays the groundwork for the industrial production of GB. Full article

The GRAS gene family, derived from GAI, RGA, and SCR, plays a crucial role in plant growth and development. In the diploid Cyclocarya paliurus (2n = 2x = 32) with heterodichogamous characteristics, 51 CpGRAS genes were identified and phylogenetically classified into 10 subfamilies. Structural analysis revealed that CpGRAS genes possessed a canonical GRAS domain, but 70% lacked introns. WGD/segmental duplication was the major driver in the expansion of the CpGRAS family. In addition, a Ka/Ks ratio below 1 for these genes implied functional constraints and evolutionary conservation. Transcriptional profiling revealed significant differential expressions of CpGRAS genes between male and female flowers from two mating types, protogyny (PG) and protandry (PA). Notably, members of the DELLA subfamily exhibited significant upregulation in female flowers at the inflorescence elongation (S3) stage. The expression level of CpSCL6-2 in late-flowering samples (PA-F and PG-M) was higher than in early-flowering ones (PA-M and PG-F). Co-expression analysis identified that CpRGL1 and CpGAI-2 of the DELLA subfamily, along with CpSCL6-2, acted as hub genes, implying their crucial roles in floral development and potential involvement in the heterodichogamous flowering mechanism in C. paliurus. These findings broaden our understanding of CpGRAS genes and provide new insights into the molecular basis of heterodichogamy. Full article

In this study, urban wastewater was treated by flocculation, ozone pre-oxidation and denitrification for efficient purification. Polymeric aluminum chloride (PAC) and polymeric aluminum ferric sulfate (PAFS) were added to the wastewater at different levels to remove the COD, turbidity, TP and TN of the wastewater. A better flocculant was selected and its optimum ozone pre-oxidation concentration was determined by changing the ozone concentration and measuring the effluent quality. Denitrification was further enhanced by varying the C/N ratio of the wastewater. The results show that, with the increase in flocculant dosage, the removal rates of COD, turbidity, TP and TN by PAC and PAFS were improved. The purification effect of PAC was better than that of PAFS and the optimum removal of COD, turbidity, TP and TN was obtained at a dosage of 80 mg L⁻¹ by PAC, at 55.9%, 55.6%, 90.0% and 13.3%, respectively. Ozone pre-oxidation enhanced the removal of COD, turbidity and TN by PAC, and the optimal ozone dosage was 1.2 mg L⁻¹, which resulted in 64.8%, 57.1% and 24.8% removal of COD, turbidity and TN, respectively. With the increase in the C/N ratio from 2.0 to 4.0, the NO₃⁻-N concentration of PAC-treated water gradually decreased, but when the C/N ratio was 4.0, the COD concentration increased, so the optimal C/N ratio should be 3.5. Overall, the combination of ozone pre-oxidation, denitrification and flocculation was an effective method to treat urban wastewater, which has a strong application prospect. Full article

A highly active alkaline phosphatase (ALP) of the protein structural family PhoA, from a mussel gut-associated strain of the marine bacterium Cobetia amphilecti KMM 296 (CmAP), was found to effectively dephosphorylate lipopolysaccharides (LPS). Therefore, the aim of this work was to perform a comprehensive bioinformatics analysis of the structure, and to suggest the physiological role of this enzyme in marine bacteria of the genus Cobetia. A scrutiny of the CmAP-like sequences in 36 available Cobetia genomes revealed nine homologues intrinsic to the subspecies C. amphilecti, whereas PhoA of a distant relative Cobetia crustatorum JO1^T carried an inactive mutation. However, phylogenetic analysis of all available Cobetia ALP sequences showed that each strain of the genus Cobetia possesses several ALP variants, mostly the genes encoding for PhoD and PhoX families. The C. amphilecti strains have a complete set of four ALP families’ genes, namely: PhoA, PafA, PhoX, and two PhoD structures. The Cobetia marina species is distinguished by the presence of only three PhoX and PhoD genes. The Cobetia PhoA proteins are clustered together with the human and squid LPS-detoxifying enzymes. In addition, the predicted PhoA biosynthesis gene cluster suggests its involvement in the control of cellular redox balance, homeostasis, and cell cycle. Apparently, the variety of ALPs in Cobetia spp. indicates significant adaptability to phosphorus-replete and depleted environments and a notable organophosphate destructor in eco-niches from which they once emerged, including Zostera spp. The ALP clusterization and degree of similarity of the genus-specific biosynthetic genes encoding for ectoine and polyketide cluster T1PKS, responsible for sulfated extracellular polysaccharide synthesis, coincide with a new whole genome-based taxonomic classification of the genus Cobetia. The Cobetia strains and their ALPs are suggested to be adaptable for use in agriculture, biotechnology and biomedicine. Full article

A synthetic flocculant of aluminum (Al) and iron (Fe) extracted from red mud (RM) has been widely used in sewage treatment, while the remaining RM residue has been ignored. This study aimed to synthesize polymeric aluminum ferric sulfate (PAFS) flocculant from RM by acid leaching and then use the acidified RM residue to produce an acid RM-based ceramsite (ARMC) by mixing bentonite, hydroxypropyl methylcellulose, and starch. Our results showed that sintering, reaction temperature, H₂SO₄ concentration, reaction time, and liquid-to-solid ratio had an obvious effect on the leaching of Al and Fe in RM, which was a necessary prerequisite for the efficient PAFS flocculants. At a PAFS dosage of 60 mg/L, turbidity and phosphate removal rates were 95.21 ± 0.64% and 89.17 ± 0.52%, respectively. When the pH value was 8.0, the turbidity and phosphate removal efficiency were 99.22 ± 0.66% and 95.98 ± 1.63%, respectively. Considering the adsorption capacity and mechanical properties, the best conditions for ARMC production included using 60% ARM and ceramsite calcination at 600 °C, with the BET surface area 56.16 m²/g and a pore volume of 0.167 cm³/g. Thermogravimetric analysis indicated that 400 °C was a reasonable preheating temperature to enhance the ARMC mechanical strength, as this temperature allows the removal of surface-adsorbed and constituent water. Under a scanning electron microscope, the ARMC appeared rough before adsorption, while relatively uniform pores occupied it after adsorption. Our conclusion will help to improve the zero-waste strategy of RM and speed up the industrial production of RM in flocculants as well as utilizing ARMC as a new type of adsorbent for phosphorus adsorption in sewage treatment. Full article

Background: The Platelet-Activating Factor (PAF)/receptor (PAFR) system is involved in asthma and allergic rhinitis; however, its role in chronic rhinosinusitis (CRS) is still unclear. This study aimed to assess the expression of PAFR and the concentration of Lyso-PAF isoforms in the nasal polyps (NP) of patients suffering from CRS with/without comorbidities such as asthma and NSAID-exacerbated respiratory disease (N-ERD) compared to healthy nasal mucosa (NM) from control subjects. Methods: NM (n = 8) and NP tissues were obtained from patients undergoing surgery for septal deviation/turbinate hypertrophy or endoscopic sinus surgery, respectively. Three phenotypes were studied: CRSwNP with no asthma (n = 6), CRSwNP with non-steroidal anti-inflammatory drug (NSAID)-tolerant asthma (n = 6), and CRSwNP with NSAID-exacerbated respiratory disease (n = 6). PAFR protein and mRNA were assessed via immunochemistry, immunofluorescence, Western blot, and real-time quantitative PCR. Lyso-PAF isoforms (C16, C18, and C18:1) were quantified via mass spectrometry. Results: PAFR protein was expressed in the NM and NP, concretely in epithelial cells and submucosal glands. Compared to NM, PAFR mRNA expression was higher in all NP phenotypes (p < 0.05) while all Lyso-PAF isoform concentrations were higher in the NP from asthmatic patients (p < 0.05). Lyso-PAF C16 and C18 concentrations were higher in the NP from asthmatic patients than in the NP from patients without asthma. Conclusions: The PAF/PAFR system could play a pathophysiological role in CRSwNP pathogenesis. Full article

(1) Background: The LEO1 (Left open reading frame 1) protein is a conserved subunit of the PAF1C complex (RNA polymerase II-associated factor 1 complex). PAF1C has well-established mechanistic functions in elongation of transcription and RNA processing. We previously showed, in fission yeast, that LEO1 controls histone H3K9 methylation levels by affecting the turnover of histone H3 in chromatin, and that it is essential for the proper regulation of gene expression during cellular quiescence. Human fibroblasts enter a reversible quiescence state upon serum deprivation in the growth media. Here we investigate the function of LEO1 in human fibroblasts. (2) Methods: We knocked out the LEO1 gene using CRISPR/Cas9 methodology in human fibroblasts and verified that the LEO1 protein was undetectable by Western blot. We characterized the phenotype of the ΔLEO1 knockout cells with FACS analysis and cell growth assays. We used RNA-sequencing using spike-in controls to measure gene expression and spike-in controlled ChIP-sequencing experiments to measure the histone modification H3K9me2 genome-wide. (3) Results: Gene expression levels are altered in quiescent cells, however factors controlling chromatin and gene expression changes in quiescent human cells are largely unknown. The ΔLEO1 knockout fibroblasts are viable but have reduced metabolic activity compared to wild-type cells. ΔLEO1 cells showed a slower entry into quiescence and a different morphology compared to wild-type cells. Gene expression was generally reduced in quiescent wild-type cells. The downregulated genes included genes involved in cell proliferation. A small number of genes were upregulated in quiescent wild-type cells including several genes involved in ERK1/ERK2 and Wnt signaling. In quiescent ΔLEO1 cells, many genes were mis-regulated compared to wild-type cells. This included genes involved in Calcium ion transport and cell morphogenesis. Finally, spike-in controlled ChIP-sequencing experiments demonstrated that the histone modification H3K9me2 levels are globally increased in quiescent ΔLEO1 cells. (4) Conclusions: Thus, LEO1 is important for proper entry into cellular quiescence, control of H3K9me2 levels, and gene expression in human fibroblasts. Full article