Browse Articles
Discover research articles across all indexed journals
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.
Driven degenerate Λ -type three-level laser with squeezed vacuum reservoir
Computational study of terahertz-driven controllable molecular isomerization
The molecular mechanism of the protective effect of tianeptine against ovarian ischemia-reperfusion injury
Dynamic birefringence and chirality of magnetically controllable assemblies of anisotropic plasmonic nanoparticles in dispersion
Abstract The ability to control the orientation and arrangement of plasmonic nanoparticles with shape anisotropy offers a promising route to achieving highly tunable optical properties. In this study, we introduce a synthetic approach for magnetically controllable plasmonic nanoparticles (MPs) consisting of an anisotropic gold core encapsulated by an iron oxide shell. The superparamagnetic property of the iron oxide shell enables rapid, reversible, and remotely controlled alignment of MPs, allowing for dynamic manipulation of their optical properties. Linearly aligned MPs demonstrate tunable transmission colors via plasmon-mediated birefringence. Helical MP arrays exhibit circular dichroism of up to 12° and g-factors reaching 0.21—the highest reported value for solution-phase assemblies of achiral nanoparticles. The synthetic method is applicable to nanoparticles of various sizes and shapes, highlighting its generality and expandability.
Impact of asymptomatic malaria infection on children’s growth in rural Malawi
Abstract Asymptomatic malaria infections are common in endemic regions, yet their impact on children’s growth remains inadequately understood. This study investigates the association between asymptomatic malaria and 6-18-month-old children’s growth indices in rural Malawi. Dried blood spots from 840 participants in Lungwena Child Nutrition Intervention 5 (LCNI-5) clinical trial were analysed at the baseline (N = 697) and every 3 months for a year. The associations between asymptomatic Plasmodium falciparum (determined by real-time PCR), and growth indices (length-for-age Z score (LAZ), weight-for-age Z score (WAZ), and weight-for-length Z score (WLZ)) were examined. Across all ages (6 to 18 months), malaria-positive children had lower mean WAZ (-1.03 vs. -0.87, 95% CI -0.17 − -0.04) and WLZ (-0.03 vs. -0.13, 95% CI -0.22 − -0.06) compared to those uninfected peers, whereas LAZ showed no significant association. However, no significant impact was observed at individual time points, except at 12 months of age. After adjusting for confounders, malaria infection remained associated with poorer children growth outcome. Asymptomatic malaria is linked to impaired growth outcomes among young children in rural Malawi. Targeted interventions aimed at managing asymptomatic malaria could mitigate growth faltering and improve child health in malaria-endemic settings.