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  • Hyponatraemia, defined as sodium concentration below 135 mmol/l, is one of the most common electrolyte imbalances. Differential diagnosis of hyponatraemia is difficult. We describe 3 cases of children with transient, severe hyponatraemia (< 125 mmol/l). While diagnosing hyponatraemia, it is of major importance to carefully ask in the anamnesis about habits related to the amount of fluid intake and the type of consumed fluids. It should also be noted that a frequent procedure during an infection is to increase fluid ingesting as a prevention of dehydration. One, however, should remember about the possibility of inducing water poisoning in a patient consuming excessive amounts of hypotonic fluids, especially when exposed to non-osmotic antidiuretic hormone stimulus, such as an acute infection or stress, and/or reduced renal excretory capacity. Only the presence of polyuria does not justify a diagnosis of arginine vasopressin deficiency (AVP-D), and especially the implementation of desmopressin treatment before all diagnostic procedures are completed, specifically in the case of hyponatraemia. Desmopressin can be used simultaneously with intravenous 3% saline solution only in the treatment of a very severe hyponatraemia, to avoid overcorrection of natraemia. In patients after profound hyponatraemia, polyuria can be observed after normalisation of fluid intake, but it is temporary.

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  • Cumulus cells play a crucial role in the oocyte growth and maturation processes through providing necessary nutrients and growth signals by gap junction communication. However, a global overview of metabolic events in goat cumulus cells is still lacking. In the present study, we collected cumulus cells from goat cumulus-oocyte complexes (COCs) at different developmental stages. Metabolomics analysis was performed to investigate the global metabolic patterns in cumulus cells during oocyte in vitro maturation. In particular, we revealed the several significantly altered metabolic pathways and metaboliccharacteristics in goat cumulus cells, including the accumulation of fatty acids, steroid hormones metabolism, active catabolism of arginine during meiotic resumption, and a progressive decline in nucleotide metabolism. In conclusion, the dataset generated by our metabolomic profiling will provide valuable information to understand the key metabolic pathways and metabolites involved in COCs development.

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  • While reactive oxygen species (ROS) have been identified as key redox signaling agents contributing to aging process, which and how specific oxidants trigger healthy longevity remain unclear. This paper aimed to explore the precise role and signaling mechanism of superoxide (O) in health and longevity.

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  • A novel smartphone-assisted fluorescent sensor based on europium/zirconium metal-organic framework (Eu/Zr-MOF) was developed for the fast and sensitive determination of doxycycline (DOX) and L-arginine (Arg). After the addition of DOX, the fluorescence of Eu/Zr-MOF was quenched owing to the inner filter effect (IFE). When Arg was introduced into the Eu/Zr-MOF@DOX complex system, the fluorescence was recovered because the interaction between Arg and Eu/Zr-MOF@DOX weakened the IFE. Moreover, the Eu/Zr-MOF produced continuous fluorescence color changes for the visual measurement of DOX and Arg. The fluorescent probe for DOX and Arg offered broad linear ranges of 0.05-80 and 0.1-60 μg/mL, respectively, with detection limits as low as 2.07 and 67.5 ng/mL. The proposed method was successfully applied to monitor DOX in eggs and Arg in human serum. This work provides a powerful platform for the real-time and visual analysis of DOX and Arg in food and biological samples.

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  • Methylation of arginine (Arg) residues on histones creates a new binding epitope, enabling recognition by aromatic cage binding pockets in Tudor domains; these protein-protein interactions (PPIs) govern gene expression. Despite their biological importance, the molecular details of methylated Arg recognition are poorly understood. While the desolvation, hydrogen bonding, and guanidinium stacking of methylated Arg have been explored in model systems and proposed to contribute to binding, direct interactions between the methyl groups and the aromatic residues in the binding pocket have not previously been investigated. Herein, we mechanistically study the CH-π interactions between the SPIN1 triple Tudor domain and histone asymmetric dimethylarginine. We find that these CH-π interactions are electrostatically tunable, exhibiting cation-π character, albeit attenuated relative to cation-π interactions with quaternary ammonium ions, offering key insight into how methylation of Arg alters its binding epitope to enable new PPIs.

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  • Effect of L-arginine on cystic fibrosis biofilms.

    Cystic fibrosis (CF) airways are L-arginine deficient which may affect susceptibility to infection with certain pathogens. The potential impact of L-arginine supplementation on , a common CF airway pathogen, is unclear. This study investigated the effects of L-arginine on biofilm cultures, using the laboratory strain PAO1 and multi-drug resistant CF clinical isolates. biofilms were grown in a chambered cover-glass slide model for 24 h, then exposed to either L-arginine alone or combined with tobramycin for an additional 24 h. Biofilms were visualized using confocal microscopy, and viable cells were measured via plating for colony-forming units. Increasing concentrations of L-arginine in bacterial culture medium reduced the biovolume of in a dose-dependent manner. Notably, L-arginine concentrations within the physiological range (50 mM and 100 mM) in combination with tobramycin promoted biofilm growth, while higher concentrations (600 mM and 1200 mM) inhibited growth. These findings demonstrate the potential of L-arginine as an adjuvant therapy to inhaled tobramycin in treating infections in people with CF.

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  • In eukaryotes, pre-mRNA splicing is vital for RNA processing and orchestrated by the spliceosome, whose assembly starts with the interaction between U1-70K and SR proteins. Despite the significance of the U1-70K/SR interaction, the dynamic nature of the complex and the challenges in obtaining soluble U1-70K have impeded a comprehensive understanding of the interaction at the structural level for decades. We overcome the U1-70K solubility issues, enabling us to characterize the interaction between U1-70K and SRSF1, a representative SR protein. We unveil specific interactions: phosphorylated SRSF1 RS with U1-70K BAD1, and SRSF1 RRM1 with U1-70K RRM. The RS/BAD1 interaction plays a dominant role, whereas the interaction between the RRM domains further enhances the stability of the U1-70K/SRSF1 complex. The RRM interaction involves the C-terminal extension of U1-70K RRM and the conserved acid patches on SRSF1 RRM1 that is involved in SRSF1 phase separation. Our circular dichroism spectra reveal that BAD1 adapts an α-helical conformation and RS is intrinsically disordered. Intriguingly, BAD1 undergoes a conformation switch from α-helix to β-strand and random coil upon RS binding. In addition to the regulatory mechanism via SRSF1 phosphorylation, the U1-70K/SRSF1 interaction is also regulated by U1-70K BAD1 phosphorylation. We find that U1-70K phosphorylation inhibits the U1-70K and SRSF1 interaction. Our structural findings are validated through in vitro splicing assays and in-cell saturated domain scanning using the CRISPR method, providing new insights into the intricate regulatory mechanisms of pre-mRNA splicing.

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  • Proper protein arginine methylation by protein arginine methyltransferase 1 (PRMT1) is critical for maintaining cellular health, while dysregulation is often associated with disease. How the activity of PRMT1 is regulated is therefore paramount, but is not clearly understood. Several studies have observed higher order oligomeric species of PRMT1, but it is unclear if these exist at physiological concentrations and there is confusion in the literature about how oligomerization affects activity. We therefore sought to determine which oligomeric species of PRMT1 are physiologically relevant, and quantitatively correlate activity with specific oligomer forms. Through quantitative western blotting, we determined that concentrations of PRMT1 available in a variety of human cell lines are in the sub-micromolar to low micromolar range. Isothermal spectral shift binding data were modeled to a monomer/dimer/tetramer equilibrium with an EC for tetramer dissociation of ~20 nM. A combination of sedimentation velocity and Native polyacrylamide gel electrophoresis experiments directly confirmed that the major oligomeric species of PRMT1 at physiological concentrations would be dimers and tetramers. Surprisingly, the methyltransferase activity of a dimeric PRMT1 variant is similar to wild type, tetrameric PRMT1 with some purified substrates, but dimer and tetramer forms of PRMT1 show differences in catalytic efficiencies and substrate specificity for other substrates. Our results define an oligomerization paradigm for PRMT1, show that the biophysical characteristics of PRMT1 are poised to support a monomer/dimer/tetramer equilibrium in vivo, and suggest that the oligomeric state of PRMT1 could be used to regulate substrate specificity.

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  • Munro ex Hook. f. is a weed of the genus ( spp.) that occurs frequently in paddy fields, causing serious harm to rice production. Florpyrauxifen-benzyl (FPB) is a foliar-applied herbicide used to control spp. in paddy fields. However, in recent years, with the widespread use of FPB in rice production, FPB-resistant barnyard grasses have been reported. Here, we identified an FPB-resistant population with a resistance index (RI) of 10.65 and conducted a comparative analysis using untargeted metabolomics and transcriptomics to investigate the differences between an FPB-resistant population and a susceptible population after treatment with the recommended field dose of FPB. Our results showed that the FPB-resistant had 115 differentially accumulated metabolites (DAMs; 65 up-regulated and 50 down-regulated) and 6397 differentially expressed genes (DEGs; 65 up-regulated and 50 down-regulated) compared to the susceptible The analysis of DAMs and DEGs revealed that DAMs were significantly enriched in Glutathione metabolism, Arginine and proline metabolism, and Zeatin biosynthesis pathways, while DEGs were mainly enriched in carbon fixation in photosynthetic organisms, photosynthesis, cyanoamino acid metabolism and glutathione metabolism, etc. The glutathione metabolism pathway was found to be significantly enriched for both DEGs and DAMs. Within this pathway, the metabolites (spermine) and genes (GSTU8, GSTU18, GSTF1) may play a pivotal role in the resistance mechanism of FPB-resistant . Furthermore, we demonstrated the presence of GST-mediated metabolic resistance in an FPB-resistant population by using NBD-Cl. Overall, our study provides new insights into the underlying mechanisms of resistance to FPB through a comparative analysis of untargeted metabolomics and transcriptomics. Additionally, we identified the GST-mediated metabolic resistance in an FPB-resistant population, and screened for three candidate genes (GSTU8, GSTU18, GSTF1), which has significant implications for improving the weed management efficacy of FPB in rice production and guiding judicious herbicide usage.

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  • Protein arginine methyltransferase 5 (PRMT5) is over-expressed in a wide variety of cancers and is implicated as having a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1. We investigated the relevance of PRMT5 and E2F1 in neuroblastoma (NB) and found that elevated expression of PRMT5 and E2F1 occurs in poor prognosis high-risk disease and correlates with an amplified Myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) gene. Our results show that MYCN drives the expression of splicing factor genes that, together with PRMT5 and E2F1, lead to a deregulated alternative RNA splicing programme that impedes apoptosis. Pharmacological inhibition of PRMT5 or inactivation of E2F1 restores normal splicing and renders NB cells sensitive to apoptosis. Our findings suggest that a sustained cancer-relevant alternative RNA splicing programme desensitises NB cells to apoptosis, and identify PRMT5 as a potential therapeutic target for high-risk disease.

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