Browse Articles
Discover research articles across all indexed journals
Experimental and numerical study of stick–slip phenomenon in granular materials
Abstract The stick–slip is a characteristic phenomenon of various mechanical systems, occurring when two bodies slide relative to each other. Friction plays a dominant role in this phenomenon, transitioning from static to dynamic when sudden movements take place. Studying this behaviour is particularly important for understanding stress transfer in granular materials. The study examines the development of the stick–slip phenomenon under plane strain conditions, which are commonly encountered in large-scale geotechnical structures. Experiments performed on glass bead samples investigate the effects of varying confining pressures, shear rates, initial void ratios, and degrees of bead wear on the development and characteristics of the stick–slip phenomenon. Additionally, a plane strain triaxial test is simulated using the discrete element method (DEM). Although the stick–slip events are not fully reproduced, some micro-slips are identified in the results. The physical mechanism underlying their development appears to correspond to the standard stick–slip behaviour reported in the experiments. Since micro-mechanical behaviour is a key to understanding the stick–slip phenomenon, incorporating DEM analyses opens a new route for determining micro-parameters and linking them to macro behaviour.
Structural basis of broad protection against influenza virus by human antibodies targeting the neuraminidase active site via a recurring motif in CDR H3
Abstract Influenza viruses evolve rapidly, driving seasonal epidemics and posing global pandemic threats. While neuraminidase (NA) has emerged as a vaccine target, shared molecular features of NA antibody responses are still not well understood. Here, we describe cryo-electron microscopy structures of the broadly protective human antibody DA03E17, which was previously identified from an H1N1-infected donor, in complex with NA from A/H1N1, A/H3N2, and B/Victoria-lineage viruses. DA03E17 targets the highly conserved NA active site using its long CDR H3, which features a DR (Asp–Arg) motif that engages catalytic residues and mimics sialic acid interactions. We further demonstrate that this motif is conserved among several NA active site-targeting antibodies, indicating a common receptor mimicry strategy. We also identified BCR sequences containing this DR motif across all donors in a healthy human repertoire database, suggesting that such precursors may be relatively common and have vaccine targeting potential. Our findings reveal shared molecular features in NA active site-targeting antibodies that can be harnessed to design broad, immune-focused influenza vaccines.
Fabrication and characterizations of 3D printed GelMA-Gel/bioactive glass scaffolds containing cerium for bone damage repair
The CCL2-CCR2 axis drives neuromuscular denervation in amyotrophic lateral sclerosis
Models for sustainable management of livestock waste based on neural network architectures
Ideal topological flat bands in chiral symmetric moiré systems from non-holomorphic functions
Dynamics and vibrational spectroscopy of quasi-one dimensional water wires inside carbon nanotubes of different diameter and chirality
Abstract Water strongly confined in nanostructures such as carbon nanotubes (CNTs) exhibits structural, dielectric, transport, dynamical and thermodynamical properties vastly different from bulk water, due to a strong modification of the (three-dimensional) hydrogen bond network. In this work, we mainly address the following aspects of extremely confined, quasi-one dimensional water chains in CNTs which have have not been emphasized much so far: The effect of chirality of the CNT, strong interactions with the hydrophobic walls and the (altered) vibrational response of confined water. Specifically, we have studied the (i) translation / diffusion, (ii) rotation / reorientation and (iii) vibrations of water chains confined within narrow carbon nanotubes (CNTs) with chirality indices (6,2), (6,4) and (6,6) using ab initio molecular dynamics. Special emphasis is on vibrational spectra, notably in the OH stretch region, obtained from fluctuations in the local OH stretching modes which were further employed to obtain two-dimensional infrared spectra and frequency-frequency correlation functions. We find that the vibrational distribution of water molecules under confinement is overall blue-shifted in comparison to bulk water, due to a breakdown of the three-dimensional hydrogen bond network. Further, the vibrational dynamics were found to dependent strongly upon the chirality and diameter of the CNTs, the latter causing stronger hydrophobic interactions with the walls of the nanotube. With respect to translational and rotational motion, the CNT-confined water molecules exhibit slower translational diffusion and faster reorientational motion compared to bulk liquid water for all cases simulated in this work.
Pre-mRNA processing factors differentially impact coordination between co-transcriptional cleavage and transcription termination
Intraarticular injection of the stromal vascular fraction for the treatment of knee osteoarthritis a prospective randomized controlled clinical trial
Acquisition of Escherichia coli carrying extended-spectrum ß-lactamase and carbapenemase genes by hospitalised children with severe acute malnutrition in Niger
Abstract Hospitalisation and routine antibiotic treatment are recommended for children with complicated severe acute malnutrition (SAM) but this may exacerbate antimicrobial resistance. Here, we investigate carriage of Gram-negative bacteria in children under five years of age receiving treatment for SAM in Niger, comparing the frequency of colonisation with bacteria carrying resistance genes at admission, during hospital stay and at discharge. E. coli isolates carrying a bla NDM-5 gene were selected for whole-genome sequencing. Rectal colonisation with bacteria carrying ß-lactamase genes is high, with 76% (n = 1042/1371) of children harbouring bacteria carrying a bla CTXM-1-group gene and 25% (n = 338/1371) carrying a bla NDM-5 gene. Over two-thirds of children who did not carry bacteria with a carbapenemase gene at admission are colonised with bacteria carrying a carbapenemase gene at discharge (n = 503/729, 69%). E. coli ST167 carrying bla NDM-5 gene is recovered from 11% (n = 144/1371) of children. Here we highlight infection control and bacterial AMR transmission concerns amongst a vulnerable population in need of medical treatment.
Green finance and environmental decentralization drive OECD low carbon transitions
The combination of active partitioning and toxin-antitoxin systems is most advantageous for low-copy plasmid fitness
Abstract Extrachromosomal and mobile genetic elements, including plasmids, and accessory chromosomes, are prevalent in all life domains. Elements integrated into the host chromosome replicate and segregate via the host life cycle. In contrast, the persistence of autonomously replicating elements relies on their ability to remain within the host population. Here, we compare the evolutionary advantage of different persistence strategies found in prokaryotic plasmids. Through intracellular competitions between plasmid genotypes, we find that the combination of active partitioning during cell division with a toxin-antitoxin (TA) system for post-segregational killing increases plasmid fitness more than either strategy alone. Mathematical modeling of long-term plasmid evolution, calibrated with empirical plasmid loss dynamics, further supports these findings. A survey of enterobacterial genomes indicates that partitioning and TA systems are core features of large plasmids. Indeed, we confirm the presence of a previously unrecognized type I TA system in conjugative IncX3 plasmids, which serve as important vectors of antibiotic resistance in human pathogens. These findings suggest that large plasmids – including conjugative and mobilizable types – encode TA systems, some of which have yet to be identified. The combination of TA and partitioning systems emerges as the most effective strategy for the evolutionary success of low-copy extrachromosomal elements.
Development of Epstein Barr virus biosensor by mimicking its infection mechanism for early detection of multiple sclerosis
Abstract Given the established link between Epstein-Barr virus (EBV) and multiple sclerosis, the early and asymptomatic detection of EBV has become increasingly important. In this study, we developed an impedimetric EBV biosensor designed for practical and early screening, based on mimicking the virus’s natural infection mechanism. To achieve this, the B cell surface protein CD21—serving as the host receptor—was immobilized onto a carbon screen-printed electrode. The interaction between CD21 and the EBV surface glycoprotein gp350 was monitored using electrochemical impedance spectroscopy. Following the optimization of experimental parameters, the biosensor’s analytical performance was evaluated. It exhibited a linear detection range from 5 to 100 ng/mL, with a limit of detection of 0.0074 ng/mL, a limit of quantification of 0.022 ng/mL, and a relative standard deviation of 1.34%. The optimized biosensor was then tested using 1:100 diluted saliva samples collected from healthy individuals, yielding highly promising results that support its potential for real-world applications.
Cryo-EM structures of ρ1 GABAA receptors with antagonist and agonist drugs
Abstract The family of ρ-type GABAA receptors includes potential therapeutic targets in several neurological conditions, and features distinctive pharmacology compared to other subtypes. Here we report four cryo-EM structures with previously unresolved ligands, electrophysiology recordings, and molecular dynamics simulations to characterize binding and conformational impact of the drugs THIP (a non-opioid analgesic), CGP36742 (a phosphinic acid) and GABOB (an anticonvulsant) on a human ρ1 GABAA receptor. A distinctive binding pose of THIP in ρ1 versus α4β3δ GABAA receptors offers a rationale for its inverse effects on these subtypes. CGP36742 binding is similar to the canonical ρ-type inhibitor TPMPA, supporting a shared mechanism of action among phosphinic acids. Binding of GABOB is similar to GABA, but produces a mixture of partially-locked and desensitized states, likely underlying weaker agonist activity. Together, these results elucidate interactions of a ρ-type GABAA receptor with therapeutic drugs, offering mechanistic insights and a basis for further pharmaceutical development.
Elucidation of crystal growth, structural characterization, thermal properties, and molecular dynamics using NMR near phase transition temperature of [N(CH3)4]2CoCl4
Multiple bursts of speciation in Madagascar’s endangered lemurs
IC2Bert: masked gene expression pretraining and supervised fine tuning for robust immune checkpoint blockade (ICB) response prediction
Abstract Bulk RNA-seq-based prediction of immune checkpoint blockade (ICB) responses has been extensively studied to distinguish responders from non-responders. However, cohort heterogeneity remains a major challenge, hindering the robustness and generalizability of predictive models across diverse RNA-seq datasets. In this study, we present IC2Bert, a novel model that employs masked gene expression pretraining combined with domain-specific supervised fine-tuning to enhance predictive robustness across heterogeneous ICB response cohorts. To ensure an objective evaluation, we assessed the model’s performance using a Leave-One-Dataset-Out Cross-Validation (LODOCV) approach. IC2Bert demonstrated significantly improved predictive accuracy and robustness compared to existing methods, effectively addressing the challenges posed by cohort heterogeneity. The IC2Bert model and its source code are publicly available on GitHub: https://github.com/data2intelligence/ic2bert.
Structure of CFTR bound to (R)-BPO-27 unveils a pore-blockage mechanism
Abstract Hyperactivation of the cystic fibrosis transmembrane conductance regulator (CFTR) contributes to secretory diarrhea, a major cause of pediatric mortality worldwide, and autosomal dominant polycystic kidney disease (ADPKD), the most common inherited cause of end-stage renal disease. Selective CFTR inhibition is a potential therapeutic strategy, with (R)-BPO-27 emerging as a promising candidate. Here, we present a cryo-EM structure of CFTR bound to (R)-BPO-27 at an overall resolution of 2.1 Å. Contrary to the previous hypothesis that it inhibits CFTR current by competition with ATP, we demonstrate that (R)-BPO-27 instead directly occludes the chloride-conducting pore while permitting ATP hydrolysis, thus uncoupling the two activities. Furthermore, we find that inhibitor binding requires some degree of NBD separation, as the inhibition rate inversely correlates with the probability NBD dimerization. These findings clarify the compound’s mechanism and provide a molecular basis for optimizing its clinical potential.