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Integrative genomic analysis of 21 orofacial diseases identifies shared genetic architecture with systemic diseases
Detection of heteroresistance in Mycobacterium tuberculosis using nanopore-based amplicon sequencing and adaptive sampling
Abstract Heteroresistance (HR) in Mycobacterium tuberculosis —the coexistence of drug-susceptible and drug-resistant subpopulations within the same host—poses a major obstacle to effective tuberculosis (TB) diagnosis, treatment, and control. The primary objective of this study was to determine whether Oxford Nanopore Technologies (ONT)-based workflows could accurately detect heteroresistance and compare their performance. To achieve this, we first optimized ONT sequencing workflows using cultured isolates and TB-positive clinical sputum, identifying phenol-based DNA extraction with ligation library as the best-performing combination, though Kit-Ligation had the best performance in amplicon sequencing from culture. We then evaluated two enrichment strategies—amplicon sequencing and Adaptive sampling (AS)—using synthetic mixtures of drug-susceptible (H37Rv) and drug-resistant (DM97) strains at defined ratios. Amplicon sequencing achieved coverage > 4,000× across target genes and reliably detected resistant alleles at frequencies as low as 1%. AS enriched 14 resistance loci with ~ 3-fold higher on-target depth compared to non-enriched nanopore whole-genome sequencing (WGS), enabling accurate detection of resistant subpopulations at 5% while retaining genomic context for lineage assignment. Together, these results demonstrate that, among the ONT workflows evaluated, nanopore amplicon sequencing provides superior sensitivity, whereas AS offers an intermediate approach, increasing depth while retaining some genomic context. These complementary approaches represent scalable strategies that could enhance TB heteroresistance detection and surveillance in high-burden settings.
Chromobox 3 assembles an epigenetic complex contributing to cystathionine γ-lyase–mediated protection against aortic aneurysm/dissection
Population-dependent agent performance in non-transitive games: a multi-agent rock–paper–scissors benchmark
Neural Response to Familiar Names Predicts Outcome of Comatose ICU Patients: A Prospective Observational Cohort Study
Preparation and characterization of self-healing nanocomposite hydrogels based on chitosan/polyethylene glycol/bacterial nanocellulose for wound dressing applications
Agricultural fungicides shape soil and sediment reservoirs of multidrug-resistant fungi
A TriNetX global collaborative network retrospective cohort study on the impact of COVID-19 vaccination on juvenile idiopathic arthritis
GPI‑anchored protein nanoclusters license migrasome expansion and serve as exocytic platforms for migrasome
Integrated geophysical, mineralogical, and geochemical investigation of gold and associated hydrothermal minerals in the Um Balad Area, Eastern Desert, Egypt
Abstract Gold exploration in structurally complex Precambrian terranes remains challenging due to the heterogeneous distribution of hydrothermal alteration zones and the difficulty of distinguishing mineralization-related structures from regional tectonic features. Recent advances in integrated geophysical interpretation have demonstrated the importance of combining multiple datasets to improve structural targeting and hydrothermal mapping within the Arabian–Nubian Shield. The Um Balad area is a promising target for gold and copper exploration, with widespread hydrothermal alteration associated with quartz veins and sulfide mineralization. This study integrates airborne magnetic data, ground gravity surveys, geochemical analyses, and mineralogical investigations to characterize the structural framework and hydrothermal alteration related to mineralization in the area. Gravity and magnetic datasets were processed to delineate lithological boundaries, structural discontinuities, and intrusive bodies associated with hydrothermal activity. Structural interpretation reveals dominant NW–SE, NNW–SSE, E–W, NE–SW, and NNE–SSW fault systems controlling fluid migration and alteration zones. Processing techniques, including radially averaged power spectrum analysis, single-body modeling, and Euler deconvolution were applied to estimate the depth extent of magnetic and gravity sources, indicating both shallow and deep-seated causative bodies. Geochemical and mineralogical analyses were conducted on representative samples from the metagabbro–diorite complex and older granitoids using Spectral Analysis (ASD) and SEM–EDX (Scanning Electron Microscopy combined with Energy Dispersive X-ray Spectroscopy). The identified alteration assemblages include hematite, goethite, muscovite, chlorite, illite, kaolinite, and ferrihydrite. SEM–EDX results indicate significant enrichment in Au, Cu, and Ag, with maximum concentrations of 5.69 wt.% Au, 1.49 wt.% Cu, and 0.22 wt.% Ag. The integration of geophysical, mineralogical, and geochemical datasets demonstrates that structurally controlled hydrothermal alteration zones represent the principal targets for gold mineralization in the Um Balad area.
CYLD-mediated lysine63 deubiquitination regulates synaptic transmission and autophagy to mitigate age-related sequelae
Abstract Lysine63 polyubiquitination is a prevalent post-translational modification in the central nervous system. Deficiency of CYLD, a lysine63-specific deubiquitinase, is linked to synaptic dysfunction and neurodegenerative disorders. However, our understanding of how CYLD contributes to the manifestation of neuronal deficits, particularly in the context of ageing, remains limited. Here, we report that CYLD-1 is essential for physiological lifespan in the nematode Caenorhabditis elegans . Neuronal CYLD-1 supports cholinergic neurotransmission and GABAergic synapse integrity, ensuring intact locomotory capacity, as well as learning and memory competence. Specifically, the deubiquitinase activity of CYLD-1 is necessary for upholding cholinergic neurotransmission and lifespan. We further show that CYLD-1 regulates autolysosomal and lysosomal network organisation in neurons and peripheral tissues in vivo. Our work unveils a crucial role of CYLD-1 in optimizing neural activity and behavioural outcomes, to improve organismal fitness and survival.
War-related stress is associated with resting-state functional connectivity of cognitive control and sensory networks in children
Discovering expert-level Nash equilibrium algorithms with large language models
Integrating multi-source remote sensing, field work, and petrography for automatic lithological mapping and mineralization potential in the Gabal El-Faraid, Egypt
Abstract The Gabal El-Faraid Group, in the Egyptian Southeastern Desert, comprises Neoproterozoic lithologies and structurally controlled mineralization zones that require an integrated exploration approach. This study integrates multi-source remote sensing data with detailed field observations, structural analysis, and petrographic investigations to improve lithological differentiation and delineate mineralization-related structures. Results indicate a potential structural-control spatial association among shear zones, hydrothermal alteration zones, and mineralization, suggesting their potential role in controlling mineralization. Support Vector Machine (SVM) and Random Forest (RF) algorithms have been used to best delineate lithological rock units of the study area. Accurate lithological mapping was achieved using an SVM applied to combined Sentinel-2 and ALOS PALSAR datasets, yielding an overall accuracy of 92.67%, a Kappa coefficient of 0.8928, and an F1-score of 88.64%. Six spectral mineral indices, like argillic, clay, ferrous silicates, ferrugination, hydroxyl, and phyllic alterations, have been emphasized using the hyperspectral PRISMA dataset. Exposed rocks comprise metavolcanics, metagabbro-diorite, tonalite-granodiorite, monzogranite, syenogranite, pegmatite, and late basic dikes, representing a multiphase magmatic sequence spanning arc-related to post-collisional stages. Structural investigations indicate a polyphase deformation history comprising four major events (D1-D4). The earliest phase (D1) is characterized by penetrative foliation, stretching lineation, and low-angle thrusting associated with nappe transport during intra-oceanic arc accretion. D2 reflects large-scale folding and regional shortening related to arc-to-continent collision. The D3 phase records transpressional strike-slip shearing, reactivating earlier structures and facilitating magma ascent, whereas D4 is marked by brittle faulting and jointing linked to post-orogenic uplift and extensional tectonics. Lineament analysis from PALSAR data highlights dominant NW-SE and NE-SW trends that closely correspond to field-measured fabrics and shear zones. Integration of field and remote sensing datasets demonstrates that late-stage deformation (D3-D4) exerted strong structural control over pegmatite emplacement, quartz veining, and hydrothermal alteration, with a main set trending WNW to NW and a less prominent set with pronounced ENE and NNW trends, emphasizing the role of inherited Pan-African structures in localizing mineralization. High-priority prospective zones in the studied granites were derived from integrated datasets, which were systematically combined in ArcGIS using a fuzzy-logic overlay. The detected zones are labeled as very high, high, moderate, low, and very low based on their potential for rare-metal mineralization. The integrated datasets can be applied to similar areas in the Eastern Desert of Egypt and across the entire Arabian-Nubian Shield (ANS).
Myosin light chain proteins cooperatively promote sarcomere growth in fast-twitch muscle
Efficiency of mining rock wastes in the removal of toxic heavy metal ions (Pb²+, Cu²+, and Cd²+) from contaminated water solutions
Abstract The Abu Tartur Plateau in the Western Desert of Egypt hosts the largest phosphate mining operation in the Middle East. Mining activities in this area generate several million tons annually of overburden waste materials, including carbonate, black shale, siltstone, glauconite, and sandstone. In the present study, phosphatic dolomite (PD) and black shale were collected from these mining wastes. Phosphatic dolomite, along with sodalite-based phosphatic dolomite (SBPD) synthesized from calcined phosphatic dolomite (CPD) and black shale, were evaluated as low-cost adsorbents for the removal of heavy metals (Pb²⁺, Cu²⁺, and Cd²⁺) from synthetic wastewater. Heavy metal contamination, particularly by Cd, Pb, and Cu, represents a major global environmental challenge. Among the available remediation techniques, adsorption is widely considered one of the most effective approaches due to its environmental sustainability, economic feasibility, and operational simplicity. The materials (PD, CPD, and SBPD) were characterized by using X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and BET surface area. Key adsorption parameters—including adsorbent dosage, pH, initial metal concentration, and contact time—were systematically investigated for Pb²⁺, Cu²⁺, and Cd²⁺ removal. The optimal adsorption performance for SBPD was achieved using a dosage of 0.2 g for Pb²⁺ and Cd²⁺, whereas PD showed optimal removal efficiencies at 0.3 g for Pb²⁺ and 0.6 g for Cu²⁺. Both adsorbents exhibited a preferential removal order of Pb²⁺ > Cu²⁺ > Cd²⁺. Kinetic and isotherm models were applied to interpret the adsorption mechanisms. The results of the present study confirm that sodalite based phosphatic dolomite (SBPD) exhibited higher metal removal efficiency than unmodified phosphatic dolomite (PD).
Proteome-wide quantification of inositol pyrophosphate-protein interactions
Abstract Inositol polyphosphates (InsPs) and inositol pyrophosphates (PP-InsPs) are highly phosphorylated signaling molecules involved in diverse cellular processes. To resolve discrete signaling events mediated by these structurally related metabolites, a mass spectrometry–based approach was developed to derive apparent binding constants on a proteome-wide scale. The method employs chemically synthesized affinity reagents for inositol hexakisphosphate (InsP 6 ) and the inositol pyrophosphates 1PP-InsP 5 , 5PP-InsP 5 , and 1,5(PP) 2 -InsP 4 (InsP 8 ). Concentration-dependent affinity enrichment combined with tandem mass tag (TMT) labeling enabled identification and quantification of ligand–protein interactions for hundreds of proteins from mammalian cell lysates. Biochemical and functional validation of selected targets demonstrated engagement with endogenous ligands. Comparison of enrichment conditions revealed a strong dependence of PP-InsP binding on Mg 2+ ions. Additionally, gene ontology analysis linked PP-InsP interactors to nuclear and nucleolar RNA processing, and subsequent analyses could identify several pyrophosphorylation sites, previously uncharacterized. In summary, these datasets provide valuable resources for exploring PP-InsP–dependent signaling pathways across biological systems.
Synergistic effects of plant growth regulators, riboflavin, and iron nanoparticles on secondary metabolites in micropropagated Ceratonia siliqua L.
Abstract Plant growth regulators (PGRs) play a crucial role in regulating the biochemical and physiological processes. Recently, nanoparticle-based approaches have attracted increasing attention for improving in vitro rooting efficiency. Ceratonia siliqua L. is a significant tree species utilized for landscaping and medicinal purposes; however, its conventional propagation is limited, making micropropagation a viable alternative. This study aimed to optimize in vitro multiplication, rooting, and secondary metabolite accumulation of C. siliqua through the use of different PGR combinations, Murashige and Skoog (MS) medium strength, and riboflavin during the multiplication stage, while evaluating the effect of iron oxide nanoparticles (Fe₂O₃ NPs) exclusively during the rooting stage. During establishment and multiplication, explants were cultured on full- or half-strength MS media supplemented with riboflavin in combination with benzyladenine (BA), naphthaleneacetic acid (NAA), and gibberellic acid (GA₃). Rooting experiments were conducted using indole-3-butyric acid (IBA; 2, 3, and 4 mg L − 1 ) applied alone or in combination with Fe₂O₃ NPs (5 and 10 mg L − 1 ). Chemical analyses were performed only on responsive multiplication treatments and compared with the mother plant. The highest shoot number (3.33 shoots per explant), shoot length (46.33 mm), and leaf number (42.67 leaves per explant) were recorded on full-strength MS medium supplemented with 1 mg L − 1 riboflavin, 1 mg L − 1 BA, 0.1 mg L − 1 NAA, and 0.1 mg L − 1 GA₃, which also resulted in the highest flavonoid content in the multiplied shootlets. For rooting, the highest rooting percentage and root number were obtained with 3 mg L − 1 IBA alone or in combination with 5 mg L − 1 Fe₂O₃ NPs. Regarding secondary metabolites, shoots on ½ MS with 1 mg L⁻¹ riboflavin and 0.5 mg L⁻¹ BA yielded high phenolic content, nearly matching the mother plant, while significantly surpassing it in DPPH antioxidant activity. HPLC confirmed this enhanced bioactivity via the unique accumulation of gallic acid, rutin, and vanillin.