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In silico comparative analysis of OXA-918 and OXA-244 sequences suggests altered beta-lactam interaction profiles in Acinetobacter baumannii and Klebsiella pneumoniae

Structural and mechanistic basis for membrane recognition and activation of the vacuolar lipase Atg15

Atg15 is a vacuolar phospholipase B essential for the degradation of intravacuolar vesicles such as autophagic bodies. Despite its central role in cellular membrane turnover, the molecular basis of how Atg15 is activated and acts on internal membranes has remained elusive. Here, by combining all-atom and coarse-grained molecular dynamics (MD) simulations with in vitro and in vivo analyses, we elucidate the structural and mechanistic principles underlying Atg15 activation and substrate recognition. Our simulations revealed that disulfide bonds are critical for maintaining the structural integrity of the catalytic core, while the C-terminal region locks the catalytic center in a closed state that prevents activation. Membrane binding induces a transition to an open state, enabling catalysis. Through MD-guided mutational analysis, we identified three regions crucial for catalytic locking, membrane binding, and substrate recognition, and experimentally confirmed that mutations in these regions inhibit activity. Furthermore, Atg15 preferentially associates with positively curved membranes, providing a potential basis for its preferential action on internal vesicular membranes. These findings suggest that Atg15’s activity is controlled through multiple regulatory layers to ensure safe and preferential membrane degradation.

The mediating role of organizational justice in the relationship between value-centered school culture and organizational citizenship: A case of North Cyprus

This quantitative research aimed to determine the mediating role of organizational justice in the relationship between teachers’ perceptions of value-centered school culture and their views on organizational citizenship. A relational screening model was utilized as the research framework. A survey was administered to 301 randomly selected teachers from general secondary education in the two largest cities of North Cyprus, Nicosia and Kyrenia. The survey consisted of four parts: A personal information form,Value-Centered School Culture Scale, Organizational Justice Scale, and Organizational Citizenship Scale. As the data showed a normal distribution, parametric tests were performed to analyze the data. In addition, the mediating role of the Organizational Justice Scale in the relationship between the participating teachers’ Values-Centered School Culture Scale scores and the Organizational Citizenship Scale scores was examined using observed-variable path analysis. The findings of this research indicated that teachers’ perceptions of values-centered school culture,organizational citizenship, and organizational justice were above average. Significant positive correlations were identified between organizational justice and organizational citizenship, as well as between organizational citizenship and a values-centered school culture. Observed-variable path analysis revealed that a values-centered school culture significantly and positively predicted organizational justice, which in turn significantly and positively predicted organizational citizenship. In addition, values-centered school culture is associated with organizational citizenship. This study offers empirical evidence that a values-centered school culture is a crucial organizational factor associated with teachers’ perceptions of organizational justice and organizational citizenship. The findings reveal that values-centered school culture has both direct and indirect effects on organizational citizenship, mediated by organizational justice. This underscores the significant role of school culture in relation to teachers’ perceptions and behaviors regarding their organization. These results expand existing knowledge by illustrating the interconnectedness of organizational culture, justice, and citizenship within educational settings. Additionally, organizational-level characteristics should be taken into account when examining teachers’ work-related attitudes and behaviors.

Colorimetric and fluorescent “turn-off” benzimidazole-derived sensor for selective detection of Cu2+ ions in real water samples and bio-imaging studies

HUWE1 targets mitochondria via RMC1 to promote neurodevelopment

The HECT-type E3 ubiquitin ligase HUWE1 is a critical regulator of protein homeostasis, genome stability, and neurodevelopment. Variants in HUWE1 are linked to X-linked intellectual disability (XLID), yet a significant number of HUWE1 variants are noncatalytic, leaving their disease mechanisms unresolved. Here, we identify an AMBRA1–RMC1–HUWE1 signaling axis that directs HUWE1-mediated ubiquitination to mitochondria to regulate neural development. In zebrafish, noncatalytic HUWE1 variants found in XLID patients (M375I, G660R, and H669Q) recapitulate key neurodevelopmental deficits, including impaired brain growth and motor neuron defects. Global ubiquitin profiling reveals that these variants selectively disrupt the ubiquitination of mitochondrial proteins without affecting nuclear substrates. Mechanistically, AMBRA1 acts as a mitochondrial scaffold that recruits RMC1, enabling HUWE1 localization to mitochondria through direct interaction with RMC1. Disruption of this recruitment by disease-associated HUWE1 variants prevents mitochondrial targeting and impairs mitochondrial substrate ubiquitination. Notably, Urolithin A treatment ameliorates neurodevelopmental phenotypes in HUWE1-deficient zebrafish. Together, our findings define an AMBRA1-organized mitochondrial recruitment pathway in which RMC1 links HUWE1 to mitochondria, explain noncatalytic HUWE1-associated XLID, and suggest mitochondrial quality-control enhancement as a potential therapeutic strategy.

Spillover effects on infant caregiving and domestic work during the poriborton clean cookstove trial

Quality care during early childhood is essential for life-long health, well-being, and productivity. Recognizing the global importance of advancing early childhood development strategies, this study conducted in-depth, face-to-face interviews with women, their husbands, and mothers-in-law to explore perceived shifts in childcare roles among participants of Poriborton Trial, a randomized controlled trial of Liquefied Petroleum Gas (LPG) cookstoves. These interviews aimed to capture diverse perspectives on evolving caregiving dynamics and explored mothers’ perspectives. Qualitative data were systematically analyzed using thematic analysis following an iterative process of coding and theme development. We found that LPG stoves facilitated notable changes in caregiving. Firstly, LPG adoption reduced cooking time and decreased workload, which increased women’s time availability for childcare. Secondly, mothers reported a greater capacity to balance household tasks and childcare, fostering more frequent interaction with their children. Thirdly, the study identified enhanced childcare practices, with LPG use enabling women to be more responsive to their children's needs particularly during illness and to maintain closer physical proximity. The adoption of LPG stoves has multiple positive impacts on the childcare roles of breastfeeding women, empowering them to engage more fully in their children’s upbringing. Building on these qualitative insights into how LPG use may enhance childcare, future quantitative research is recommended to rigorously assess outcomes such as reductions in maternal stress, increased time availability for mothers, and changes in mother-child attachment attributable to LPG stove adoption.

Impact of iridocorneal angle on aqueous humor flow after implantable collamer lens placement by numerical simulation analysis

High-coverage ancient genomes reveal divergent population histories and prehistoric starch-related genetic variation in Japan

Prehistoric population movements played a central role in shaping the genetic diversity across Eurasia. As the eastern terminus of the Eurasian continent, the Japanese archipelago provides a pivotal context for reconstructing the genetic interplay between prehistoric indigenous lineages and continental migrations. However, high-resolution genomic evidence from mainland Japan is limited due to poor DNA preservation. In the present study, we report two low-contamination, high-coverage ancient genomes from mainland Japan, namely an Initial Jomon individual (>67-fold) and a Middle Yayoi individual (>46-fold). The genomes enabled diploid genotyping and individual-level demographic inferences at unparalleled resolutions. Demographic reconstructions revealed that while both lineages underwent population contractions during the Last Glacial Maximum (LGM), their subsequent trajectories diverged; the Jomon lineage was characterized by long-term postglacial stability with no discernible expansion, whereas the Yayoi-related ancestral population exhibited gradual and sustained growth. Our analysis further identified a distinct genetic continuity between the Middle Yayoi and present-day mainland Japanese, refining the evolutionary trajectory of modern genetic profiles. Furthermore, the genomic profile of the Yayoi individual reflected a complex ancestral background shaped by continental interactions before their arrival on the archipelago. Notably, the higher salivary amylase ( AMY1 ) copy number observed in the Initial Jomon individual suggests that AMY1 copy number variation, potentially relevant to starch-rich diets, was already present before the large-scale expansion of rice farming in the Japanese Archipelago. Collectively, the findings demonstrate that high-coverage ancient genomic approaches can provide a powerful framework for deciphering the contrasting population histories and evolutionary trajectories of human lifestyles.

Beyond physical fitness: Pre-to-post hematological and physical fitness changes during an eight-week multi-component exercise program in sedentary adults aged 30–45 years

This exploratory study aimed to examine pre-to-post changes in physical fitness and selected hematological parameters during an 8-week multi-component exercise program in sedentary adults. The study used a single-group pre-test/post-test quasi-experimental design to describe temporal changes within the same participants. Thirty-six sedentary volunteers (15 females and 21 males) aged 30–45 years completed a multi-component program including cardiorespiratory endurance, strength, balance, and flexibility exercises for 45–50 minutes per session, 3 days per week, for 8 weeks. Paired-samples t-tests were used to compare pre-test and post-test measurements. Body weight and body mass index decreased, whereas estimated VO 2 max, vertical jump, flexibility, speed, agility, and balance performance showed statistically significant pre-to-post changes (all p < 0.001). Significant increases were also observed in hemoglobin, hematocrit, erythrocyte, leukocyte, and platelet values (all p < 0.001), whereas MCV and MCH did not change significantly (p > 0.05). Participation in the program coincided with favorable changes in body composition and physical performance and with measurable changes in selected hematological parameters. However, the absence of a control group and the lack of direct assessment of plasma volume, hydration status, erythropoietin, iron status, and hemoglobin mass preclude causal and mechanistic conclusions. The hematological findings may partly reflect hemoconcentration, plasma-volume shifts, or other physiological variation and should therefore be interpreted cautiously.

Effects of emotion and emotional congruence on the multisensory temporal binding window during audiovisual speech integration

Measurement accuracy in mechanobiology: A unifying statistical framework for testing cellular forces

Mechanobiology is gaining traction as it reveals the fundamental role of physical forces and mechanical stress in biological function. Because physiologically relevant experiments are often inaccessible to direct physical probes, forces and stress at the microscale are increasingly estimated via multistep, image-based inverse problems such as Traction Force Microscopy. However, these measurements typically lack essential statistical descriptors such as error bars, CI, or P -values, limiting their reliability in experimental science. We present a single-step reconstruction framework that unifies a broad class of image-based inverse methods in mechanobiology under a general formulation that enables uncertainty quantification. This includes the visualization of high-dimensional credible regions, as well as an original formalization of abstract experimental questions into hypothesis tests. Overall, our work systematizes the development of new measurement techniques and contributes rigor and interpretability to image-based quantification in biophysical systems.

Design of a novel epitope-based tetravalent subunit vaccine against dengue virus: An immunoinformatic approach

Dengue imposes a profound global impact, with millions affected annually. Its transmission by Aedes mosquitoes poses significant challenges to combat, aggravated by urbanization and climate change. Despite efforts, no impeccable antiviral treatment exists to date, highlighting the urgency for a vaccine. Developing one encounters hurdles like the four distinctive serotypes of the virus and complex immune responses. In this study, we employed an immunoinformatics approach to design an epitope-based tetravalent subunit vaccine aimed at confronting all DENV serotypes. The study contemplates epitope prediction and screening, physicochemical assessment, molecular docking, molecular dynamics (MD) simulations, immune simulations, and in silico cloning. The vaccine construct comprises human β-defensin 3 adjuvant and 23 epitopes joined with linkers. Notably, the vaccine has an antigenicity of 0.9319 with 97.35% population coverage worldwide. Molecular docking with toll-like receptor 2 (TLR2) and TLR4 showed promising interactions with lowest energies of −1240.5 kJ/mol (76 members) and −1393.3 kJ/mol (40 members), respectively, exhibiting significant electrostatic, van dar Waals, and other interactions. Molecular dynamics (MD) simulations of 200 nanoseconds revealed the vaccine to be stable and flexible with the receptors. The solvent accessibility and radius of gyration were also in suitable ranges. The three-dose vaccine regimen elicited a robust and durable multi-lineage immune response, characterized by stable B and T-cell memory, sustained surveillance, and high-titer antibody production (IgM/IgG) alongside a pro-inflammatory cytokine profile (IFN-γ and IL-2) for effective antigen clearance. These findings suggest that our vaccine outperforms any other Dengue vaccine developed to date. However, since this study was conducted through in silico methods, in vitro and in vivo validations are required to confirm the vaccine as a potential candidate for clinical trials.

Evaluating the significance of platelet count, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in critically ill children

Abstract When critically ill pediatric patients are admitted to the pediatric intensive care unit (PICU), they may face significant morbidity and mortality. Therefore, it is essential to identify at-risk patients early to manage their conditions promptly and navigate through the complexities of their illnesses. This study aims to evaluate the prognostic value of platelet count, Neutrophil/Lymphocyte ratio (NLR) and the Platelets/Lymphocyte ratio (PLR) in children undergoing medical care in the PICU.Over a period of 6 months, a prospective study involving 91 PICU patients was conducted. Upon admission, patients underwent detailed history-taking, comprehensive systemic evaluations, and standard laboratory tests that encompassed complete blood counts, C-reactive protein levels, coagulation profiles, as well as liver and kidney function assessments. Subsequently, the NLR and PLR values were determined. The median NLR was slightly elevated in non-survivors compared to survivors, whereas the PLR was higher in survivors, although these differences were not statistically significant. Platelet levels emerged as a predictive factor for mortality, with an AUC of 0.748, a cutoff value of 244.5, and a p-value of 0.002. Additionally, NLR showed a negative correlation with the Glasgow coma score and a positive correlation with age, TLC, CRP, and ALT, with correlation coefficients of ( r =-0.253, p  = 0.016), ( r  = 0.320 , p  = 0.002), ( r  = 0.292, p  = 0.005), ( r  = 0.242 , p  = 0.027), and ( r  = 0.256 , p  = 0.028) respectively. While no statistically significant relationship was observed between NLR and PLR and non-survivors, platelet count showed moderate discriminatory performance for prognostic evaluation and may be used as part of early risk stratification in critically ill patients.

Stabilization of recurrent neural networks through divisive normalization

Stability is a fundamental requirement for both biological and engineered neural circuits, yet it is surprisingly difficult to guarantee in the presence of recurrent interactions. Standard linear dynamical models of recurrent networks are sensitive to the precise values of the synaptic weights, since stability requires all eigenvalues of the recurrent matrix to lie within the unit circle. Here we demonstrate, both theoretically and numerically, that an arbitrary recurrent neural network can remain stable even when its spectral radius exceeds 1, provided it incorporates divisive normalization, a dynamical neural operation that suppresses the responses of individual neurons. Sufficiently strong recurrent weights lead to instability, but the approach to the unstable phase is preceded by a regime of critical slowing down, a well-known early warning signal for loss of stability. Remarkably, the onset of critical slowing down coincides with the breakdown of normalization, which we predict analytically as a function of the synaptic strength and the magnitude of the external input. Our findings suggest that the widespread implementation of normalization across neural systems may be linked to its essential role in ensuring dynamical stability in the presence of the strong recurrent interactions required for complex cortical computations.

‘Pilot RCT of a new treatment for child conduct problems that have not responded to evidence-based parent training’

Background Children with conduct problems are at high risk of persisting mental health problems, making them a priority for early intervention. Group-based parent-training is effective but with a substantial failure rate. Based on evidence on the value of involving children, we developed Reflective Interpersonal Therapy for Children and Parents, (RICAP). We report feasibility and outcomes from the first pilot trial of an intervention for children with conduct problems persisting after parent training. In contrast to most studies, we used both parent and teacher report. Methods The sample comprised 105 children and their parents aged 4–10 years inclusive referred to UK Child and Adolescent Mental Health Services (CAMHS) with conduct problems. All were offered the Incredible Years (IY) parent training intervention, and parents provided pre- and post-treatment measures (including CBCL, SDQ). Children still above clinical threshold after IY were randomized either to RICAP or to usual CAMHS treatment (CTAU) with follow up 8 months later. Only those randomized to CTAU could receive school-based interventions. Trial Registration Number: ISRCTN25252940. Results Feasibility was supported by high retention through the initial IY (102/105) and subsequent RCT phases of the study (58/70 eligible for randomization). The majority of those randomized to RICAP attended for 11/14 or more sessions, reflecting its high acceptability to both children and parents. By parent report RICAP was superior to CTAU on CBCL externalising (d = 0.32) and internalising (d = 0.42) problems, while by teacher report CTAU was superior on SDQ total problems (d = 0.32) and reactive aggression (d = 0.27). Conclusions We provide first evidence of the feasibility of a design in which non-responders to parent training are randomized to novel intervention or control conditions. Outcomes were different for parent and teacher reports, highlighting for future randomized controlled trials the need to attend to possible reporter and treatment context variations.

Retraction Note: A randomized clinical trial of erector spinae plane block and chronic pain after posterior lumbar surgery

Equilibrium and stability of coupled nonlinear energy-storing components

Coupled systems of nonlinear components occur across physics and engineering and can display rich behaviors such as multistability, snap-through, and memory. These phenomena play a key role in physical intelligence, where functional behavior emerges from structure rather than algorithmic control. Yet, predicting the equilibrium states and stability of these systems is challenging due to intricate energy landscapes and the presence of multiple, often disconnected, equilibria. Here, we introduce a general static framework based on a parametric space in which each point represents an element-level equilibrium. In this space, system-level equilibria appear as a one-dimensional manifold, enabling their visualization without the ambiguities that appear in conventional displacement maps. By combining this formulation with a continuation strategy and a local stability assessment, the method traces both stable and unstable equilibria, including isolated isolas inaccessible by standard loading paths. We validate the method experimentally in the mechanical domain using coupled nonlinear-spring and inflatable systems, achieving quantitative agreement between predictions and measurements. This unifying approach offers a powerful tool for the design and analysis of nonlinear coupled systems, enabling systematic exploration of their equilibrium landscapes across disciplines.

Stability of grain and fodder yields in extra-early cowpea genotypes in Southeastern Niger

Cowpea [ Vigna unguiculata (L.) Walp.] is a vital food and fodder crop in Niger, but its productivity is constrained by drought, poor soils, striga and pest pressures. Developing extra-early dual-purpose varieties is essential for strengthening food and feed security in these fragile production zones. This study evaluated the effects of genotype, environment, and their interaction on the stability of grain and fodder yields in 21 cowpea genotypes tested across six environments using an alpha-lattice design with three replications. Stability was assessed through Shukla’s stability variance, the cultivar superiority index, Wricke’s ecovalence, GGE biplot, and the multi-trait genotype–ideotype distance index (MGIDI). Results revealed significant differences among genotypes, environments, and genotype × environment interactions for all traits; environmental effects had the highest mean squares for all traits (p < 0.001). Broad-sense heritability ranged from 0.77 (fodder yield) to 0.88 (days to 50% flowering), and genetic advance as percentage of mean was high for yield traits (GAM = 78.67% for pod yield, 81.80% for grain yield, 99.59% for fodder yield), indicating strong selection potential. Mean grain yield across all genotypes and environments was 1,394.32 kg ha ⁻ ¹, and the coefficient of variation ranged from 26.59% (GY) to 40.63% (FY). Notably, ten extra-early lines—BM22, BP02, BP15, MM142, 65B5080, BP18, BM21, BM13, MM141, and BM12—were identified as combining early maturity with high and stable grain and fodder yields. These lines should be further evaluated across diverse agroecological zones to confirm their adaptability and alignment with farmer preferences, prior to deployment as released varieties or as parents in cowpea improvement programs targeting climate-resilient, dual-purpose productivity in the Sahel.

Retraction Note: Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus

The multilayered cuticle underlying structural coloration in red algae shares features with the metazoan extracellular matrix

Structural coloration, a physical phenomenon observed in many living organisms, may arise from the interference of light with highly organized surface nanostructures. In some seaweeds, these nanostructures consist of cuticular lamellae in the outer part of the extracellular matrix (ECM) of the epidermis. However, the chemical composition of seaweed cuticles is poorly understood and the molecular components of lamellae remain unidentified. Here, we use integrated genomic, transcriptomic, proteomic, and metabolomic approaches together with analytical profiling of carbohydrates to determine the composition of the multilayered cuticle in the red alga Chondrus crispus and assess its evolutionary conservation. The structural assembly reveals common features with the ECM of animals. The carbohydrate fraction includes a complex mixture of carrageenans and glycosaminoglycan-like compositions. A major von Willebrand factor A domain protein, Lamellae Cohesive Protein, plays a critical role in protein–protein interactions and binding to sulfated polysaccharides. We have further identified the major proteins of the algal cuticle, providing a framework for addressing the evolutionary origins of the cuticle and raising important questions regarding its role, particularly across the red algal life cycle marked by major structural differences in its ECM.