Browse Articles

Active zone plasticity couples sleep need to presynaptic hypophosphorylation

Sleep need is associated with both circuit dynamics and widespread synaptic plasticity, yet the specific synaptic changes underlying sleep homeostasis remain incompletely understood. In Drosophila , sleep loss has been shown to trigger plasticity of the presynaptic active zone, marked by increasing levels of the ELKS-family scaffold protein Bruchpilot (BRP). By titrating brp gene copy number, we previously established a presynapse-specific, dosage-dependent paradigm that modulates sleep pressure. Here, to elucidate the molecular landscape of this plasticity, we performed synapse-enriched integrated-omics. Proteomic and bioinformatic analyses revealed changes in immune and stress response pathways and local translation control. Strikingly, phospho-proteomic analysis uncovered a global shift toward hypophosphorylation, particularly in presynaptic proteins, indicating a reprogramming of the phosphorylation–dephosphorylation balance. This presynaptic hypophosphorylation is likely contributed by reduced activity of Protein Kinase A (PKA) and enhanced substrate affinity of Protein Phosphatase 1 (PP1) mediated by its regulatory subunit Spinophilin (Spn). Manipulating either PKA or PP1 activity was sufficient to suppress BRP-modulated sleep phenotypes. We propose that presynaptic hypophosphorylation constitutes a molecular signature of local synaptic remodeling that adaptively tunes sleep need via reversible posttranslational modification, a mechanism likely conserved across species.

A two stage statistical framework for cold start spare part demand forecasting

Accurate demand forecasting for spare parts under true cold-start conditions remains a fundamental challenge due to extreme demand sparsity, zero inflation, and the complete absence of historical demand information. Conventional time-series methods, single-stage machine learning models, and sequence-based probabilistic forecasters are inherently ill-suited to this setting, as they either rely on historical observations or fail to properly represent zero-demand events and distributional uncertainty. To address this gap, this study proposes a novel Zero-Inflated Gamma Monte Carlo (ZIG MC) framework that explicitly decomposes demand into occurrence and magnitude components and generates fully probabilistic forecasts suitable for risk-aware inventory decision-making. The proposed approach integrates a Bernoulli classifier for demand occurrence with a Gamma-based magnitude model and employs Monte Carlo simulation to construct predictive demand distributions. Model performance is evaluated using a strict part-level nested cold-start validation protocol on an industrial transactional dataset, ensuring genuine generalization to previously unseen parts. Results demonstrate that ZIG MC consistently outperforms strong single-stage regressors, statistical hurdle models, and a state-of-the-art probabilistic deep learning benchmark (DeepAR). The proposed framework achieves the lowest point forecast error (MAE = 5.65), representing a 6.4% improvement over the strongest single-stage baseline, while also delivering superior scale-independent accuracy (MASE = 0.87). Probabilistic evaluation using the Continuous Ranked Probability Score shows an order-of-magnitude improvement over DeepAR (CRPS = 3.27 vs. 15.41), indicating substantially better calibration and sharper predictive distributions under cold-start conditions. Quantile-based reliability analysis confirms that predicted service-level quantiles are well aligned with empirical outcomes, enabling reliable translation of forecasts into inventory policies. Statistical significance testing further confirms that the observed performance gains are robust and not attributable to random variation. Sensitivity analyses demonstrate that forecasting performance is stable with respect to distributional assumptions and Monte Carlo sampling size. Inventory simulations reveal that ZIG MC yields higher fill rates and lower stock-out risk than competing probabilistic models at comparable inventory levels, directly linking improved probabilistic calibration to operational benefits. Collectively, these findings establish ZIG MC as a robust and practical framework for cold-start forecasting of intermittent demand, offering a principled foundation for uncertainty-aware inventory planning in data-scarce environments.

Effects of pharmacological modulation of cortical excitability on resting-state EEG PAC in humans

Abstract Electroencephalography (EEG) signal is driven by oscillations arising from the synchronized activity of cortical neuronal populations. Phase-amplitude coupling (PAC) refers to the interaction whereby the amplitude of higher-frequency oscillations is systematically modulated by the phase of slower rhythms. It has been suggested that the excitation/inhibition (E/I) balance, which is often disrupted in neuropsychiatric and neurodegenerative disorders, plays a critical role in shaping PAC, although direct evidence in humans remains limited. In this study, we investigated the effects of pharmacologically modulated E/I balance on PAC using resting-state EEG (rs-EEG) data. Specifically, we analyzed the impact of anti-glutamatergic drugs, dextromethorphan (NMDA receptor antagonist) and perampanel (AMPA receptor antagonist), as well as nimodipine (L-type voltage-gated calcium channel blocker) on PAC in a double blind, placebo-controlled experiment. Analysis revealed a significant decrease in PAC following administration of dextromethorphan and perampanel, while nimodipine and placebo showed no effects. By showing that PAC is sensitive to pharmacological modulation consistent with shifts in cortical E/I balance, this study confirms its physiological relevance and supports its use as a biomarker of excitability disturbances and cortical dysfunction across neurological and psychiatric disorders.

Madhav Gadgil (1942–2026): A pioneering Indian ecologist’s legacy of biodiversity conservation and human coexistence

Madhav Gadgil was an evolutionary ecologist and champion of governmental and intergovernmental policies for biodiversity conservation, human coexistence with nature, and indigenous rights to land, natural resources, and self-governance. He made foundational contributions to the development of biodiversity sciences, human ecology, people’s traditional knowledge—and inherent rights to that knowledge as documented through biodiversity registers. Gadgil advocated a coherent policy integrating human welfare and biodiversity conservation in India. He will be remembered as an academic giant and an unmatched thinker, policy advocate, institution-builder, and humanitarian.

Research on the influencing factors and mechanism of AR e-commerce consumers’ purchase intention

Against the backdrop of the digital economy and the increasing integration of virtual and physical consumption scenarios, augmented reality (AR) e-commerce reshapes the shopping experience by overlaying virtual information onto real-world contexts, thereby accelerating the industry’s shift from traffic-driven competition to experience-based competition. However, existing studies remain insufficient in explaining the underlying mechanism through which AR e-commerce influences consumers’ purchase intention, and the applicability of the stimulus–organism–response (S–O–R) framework in virtual–real integrated environments has not been adequately extended. Drawing on the S–O–R paradigm, this study conceptualizes four key AR-enabled characteristics—immersive virtual try-on, interactive product display, real-time fusion shopping, and personalized recommendation—as stimulus variables (S). Perceived value and brand attitude are modeled as organism variables (O), and purchase intention is treated as the response variable (R), forming an integrated conceptual model. Using survey data collected from 482 valid respondents, structural equation modeling (SEM) is employed to test the proposed relationships. The results indicate that all four AR stimuli indirectly enhance purchase intention by positively affecting perceived value and brand attitude. Among the stimulus dimensions, real-time fusion shopping exerts the strongest positive effect on perceived value (β = 0.290), whereas personalized recommendation shows the most pronounced effect on brand attitude (β = 0.295). In addition, perceived value and brand attitude play partial mediating roles, and brand attitude demonstrates a stronger direct effect on purchase intention (β = 0.449) than perceived value (β = 0.347). Theoretically, the present study systematically translates AR e-commerce technological attributes into stimulus dimensions within the S–O–R framework, thereby extending its explanatory boundary in virtual–real integrated settings and offering an integrated “technology–scenario–behavior” analytical lens. Practically, the findings provide actionable insights for e-commerce platforms and brand managers seeking to optimize AR-driven experience design and improve conversion outcomes.

Omics signature of new-onset mild cognitive impairment and dementia in a population-based study

Avoidance of MAIT cells is an essential determinant of <i>Listeria</i> monocytogenes pathogenesis

Mucosal-associated invariant T (MAIT) cells are among the most conserved and abundant innate-like T cells in humans that recognize microbial-derived riboflavin precursors and elicit potent antimicrobial responses. The foodborne pathogen Listeria monocytogenes is a broad host-range facultative intracellular pathogen that lacks the riboflavin biosynthetic pathway, leading us to hypothesize that this deficiency is pathoadaptive and allows the pathogen to evade MAIT cells. Here, we show that L. monocytogenes strains engineered to produce riboflavin ( L. monocytogenes - ribDEAHT ) are attenuated in wild-type mice but fully virulent in MAIT cell–deficient mice. Infection with L. monocytogenes - ribDEAHT prompted rapid and robust MAIT cell expansion in multiple tissues and required the cytolytic effector perforin to eliminate infected cells in vivo and in vitro. We also assessed the therapeutic potential of L. monocytogenes - ribDEAHT- stimulated MAIT cells in both infectious disease and cancer mouse models. Therapeutic administration of L. monocytogenes - ribDEAHT provided protection against Francisella tularensis in the lungs and inhibited tumor growth even in the absence of CD8 + T cells. These findings reveal the importance of MAIT cell evasion during L. monocytogenes infection and highlight the therapeutic potential of engineered L. monocytogenes to activate and harness MAIT cells for protection against infectious disease and cancer.

EMP: Enhanced Multi-modal Prediction for fashion sales using Fourier Mapping and ERP-based contrastive learning

Predicting sales for newly introduced fashion products presents a significant challenge due to the absence of historical data and the inherently multi-modal nature of the inputs. To address this issue, we propose the Enhanced Multi-modal Prediction (EMP) model, a novel framework for zero-shot time series forecasting. EMP follows a two-stage architecture: (1) ERP-Aware Contrastive Learning, which retrieves reference items using Edit Distance with Real Penalty (ERP), a metric-based elastic distance designed to measure similarity between real-valued time series, to construct a meaningful embedding space, and (2) a Transformer-based encoder-decoder, which predicts 12-week sales trajectories using Fourier-mapped embeddings. Unlike prior models that rely on external signals, EMP leverages internal reference item sales, thereby eliminating dependency on third-party APIs and enhancing forecasting accuracy. It introduces Fourier Mapping, which generates scale-aware embeddings that preserve the absolute magnitude of sales values while enabling interpretability through inverse mapping. This representation mitigates spectral bias and allows the model to effectively capture both low- and high-frequency sales patterns. To maximize this benefit, Fourier Mapping is applied selectively to internal reference item sales, where high frequency variation is more prominent than in external signals. We further present a theoretical analysis of the Lipschitz continuity of Fourier Mapping, demonstrating that it maintains a higher Lipschitz constant than conventional scaling methods. This property ensures the preservation of fine-grained input variations, thereby improving the model’s sensitivity to subtle fluctuations in sales trajectories. Experiments on both private and benchmark datasets demonstrate that EMP achieves superior forecasting accuracy compared to existing methods, validating its effectiveness in fashion sales prediction. The implementation of our method is available at the following URL: https://github.com/sanguk-ys/EMP .

Incorporating dataset-level semantic priors into large language models for environmental time-series forecasting: a soil moisture and temperature case study

Cryopreservation through vitrification enables functional recovery of the mouse hippocampus

Editorial Note: “In Weapons We Trust?” Four-culture analysis of factors associated with weapon tolerance in young males

Pythagorean fuzzy time series approach based on hybrid high-order artificial neural network for nonlinear time series forecasting

<i>Arabidopsis</i> YEATS domain proteins facilitate DNA double-strand break repair via homology-directed pathways

DNA double-strand break (DSB) repair is required to maintain genome integrity and organismal fitness. This process occurs within chromatin and although accurate repair requires extensive changes in chromatin structure and composition, chromatin effectors facilitating DSB repair remain largely unknown in plants. Using reverse genetics, we identified two chromatin readers, YAF9A and YAF9B, as new factors required for DSB repair in Arabidopsis . While only YAF9B is induced by DNA damage, both YAF9A and YAF9B are required for DSB repair, including via homology-directed repair pathways. Mechanistically, we found YAF9A and YAF9B denote distinct remodeling complexes: While YAF9A associates with both NuA4 and SWR1, YAF9B only associates with NuA4, defining a DNA-damage-specific version of this remodeling complex and linking NuA4 to DSB repair in plants. We also uncovered direct roles for YAF9A and YAF9B in DNA repair, rather than indirect roles in gene regulation, as yaf9 mutants showed normal transcriptional responses to DNA damage. Finally, we demonstrate that the YAF9B reader domain is required for DSB repair. These results link YAF9A, YAF9B, and their respective remodeling complexes, to DSB repair in a histone reader-dependent manner, expanding our understanding of how chromatin effectors regulate DSB repair in plants.

Navigating the unspoken: A qualitative study of employees’ perceptions of culture and norms surrounding sexual harassment at a Swedish university

Sexual harassment persists in academic workplaces despite extensive policy frameworks. This study explored how employees at a large Swedish university perceive and articulate the organisational culture and everyday norms that shape sexual harassment. Ten focus group discussions were held with forty staff members, separated by managerial role and conducted in Swedish or English. Transcripts were analysed using qualitative content analysis to identify shared meanings, latent themes and interpretive patterns. Analysis generated one overarching theme, perceiving sexual harassment through the lens of organisational silence, power relations, and negotiated boundaries, supported by four sub-themes. Participants described boundary-setting as a collective, situational process: definitions of harassment shifted in real time, with women often seeking peer confirmation while men framed the same conduct as innocuous. Formal and informal hierarchies amplified this ambiguity: senior researchers with grant-generating prestige were deemed ‘untouchable’, and managers reported uncertainty about how to act without clear procedural guidance. Silence emerged as a strategic response to protect careers and collegial relationships, normalising borderline behaviours through humour and rationalisation. Yet employees also engaged in discrete forms of peer solidarity, staying with vulnerable colleagues after meetings, quietly redirecting collaborations, which signalled a sense of collective responsibility even in the absence of robust institutional support. These findings show that policy compliance alone cannot shift workplace culture when interpretive authority rests with peer groups and incentive structures reward silence. Universities therefore need to focus on organisational level responses that equip leaders with emotional competence and procedural clarity and support the creation of a work environment that can identify, prevent, and respond to sexual harassment. Embedding such measures can transform informal solidarity into a shared, institutionally endorsed standard of respect.

Adversarial sample generation technology combining benign salient areas and improved GAN in white-box and black-box attack scenarios

A long-distance signaling loop promotes soybean nodulation and productivity

Legume nodulation is initiated when soil bacteria rhizobia infect root hairs and is tightly regulated by host-derived mechanisms that restrict nodule numbers to balance the benefits of symbiotic nitrogen fixation with the plant’s growth and metabolic demands. However, how plants actively promote the initiation of nodulation to counterbalance these restrictive mechanisms and maintain an optimal level of nodulation remains largely unknown. Here, we report a systemic regulatory mechanism through which soybean ( Glycine max ) promotes rhizobial infection. We show that inoculation of soybean roots with rhizobia suppresses the biogenesis of microRNA miR4416-5p in shoots, a mobile microRNA that is transported from shoots to roots. The resulting reduction of miR4416-5p levels in roots enhances the expression of a vegetative lectin gene Lectin 3 ( GmLe3 ), which promotes rhizobial infection, thereby enhancing nodule formation and improving plant productivity under low nitrogen conditions. We further demonstrate that suppression of miR4416-5p biogenesis in shoots is triggered by the root-derived C-TERMINALLY ENCODED PEPTIDE 7 (GmCEP7), establishing a long-distance GmCEP7-miR4416-5p- GmLe3 regulatory loop that is critical for desirable symbiotic synergy and plant productivity. Comparative genomic analysis reveals that this miR4416-5p-mediated regulatory module is absent in the model legumes Medicago truncatula and Lotus japonicus but appears to be conserved in economically important legume crops common bean ( Phaseolus vulgaris ) and pigeonpea ( Cajanus cajan ), suggesting an evolutionary innovation in nodulation control. These findings uncover a systemic mechanism that promotes rhizobial infection and highlight an evolutionary innovation in regulation of nodulation with potential implications for improving legume crop productivity under nitrogen-limited conditions.

Student-teacher agreement on personality traits and social competencies during early adolescence: A longitudinal study

The present study sought to validate existing knowledge on inter-rater agreement on personality traits and social competencies. Based on longitudinal data, the study aimed to determine whether the agreement between student and teacher reports changes over time. The research sample consisted of a total of 296 early adolescents (181 females, 115 males, average age in the first wave of the two-year study period was 12.37 years). The personality traits and social competencies of students were rated by class teachers (N = 28, 75% females). Personality traits were measured by the Big Five Inventory and social competencies by the Social Skills Improvement System. The main findings of the study are as follows: 1) the highest agreement between student and teacher ratings of personality traits and social competencies was found for characteristics that were high in observability; 2) there was greater agreement between student and teacher ratings of social competencies for girls; 3) high temporal stability was found for personality traits and social competencies for both students and teachers; there were no substantial changes in the agreement of student and teacher ratings over time. Attention to hidden or difficult-to-assess student characteristics may prevent developmental, school, and social/interpersonal problems in adolescents.

Sustained Notch activation depletes adult neural stem cells and impairs cognitive function

A pericyte chloride clamp mechanism governs capillary control of cerebral blood flow

Thin-strand pericytes cover the deepest reaches of the brain’s capillary network, and their fine processes are intimately associated with adjacent endothelial cells (ECs). Recent work has revealed that thin-strand pericytes contribute to electrical signaling throughout the brain’s vasculature by generating hyperpolarizing signals that can be transmitted over long distances to relax remote ensheathing pericytes around proximal branches of the capillary bed and smooth muscle cells (SMCs) around arterioles, thereby eliciting blood flow increases. Resetting hyperpolarizing events in thin-strand pericytes must involve the engagement of ion channels that carry depolarizing currents, but the channels that mediate such conductances are unknown. Here, we reveal that thin-strand pericytes of the mouse cortex express functional TMEM16A calcium (Ca 2+ )-activated chloride (Cl − ) channels (CaCCs) encoded by the Ano1 gene, and we demonstrate that these are controlled by endoplasmic reticulum (ER) Ca 2+ release through ryanodine receptors (RyRs) and inositol-1,4,5-trisphosphate (IP 3 ) receptors (IP 3 Rs), and Ca 2+ entry via plasmalemmal L- and T-type voltage-dependent Ca 2+ channels (VDCCs). We show that the activity of thin-strand pericyte CaCCs plays a key role in tethering membrane potential close to E Cl to regulate upstream arteriole diameter in vivo. We term this mechanism the pericyte “Cl − clamp,” and we show that this functions to oppose hyperpolarizing electrical signaling and dilation under basal conditions and conversely opposes constriction under depolarizing conditions. We suggest that the operation of this VDCC-ER-CaCC unit is thus essential for optimal management of energy substrate delivery to local neurons.

Calcitonin as an adjunct for phantom limb pain

Objective This retrospective study evaluated calcitonin as an adjunct therapy for reducing phantom limb pain (PLP) following lower limb amputation. Method The study included 35 patients who received at least 3 days of calcitonin treatment between January 1, 2017, and December 31, 2023. We collected demographic data and pain ratings (intensity, distress, and interference with activity) before and after calcitonin treatment. Descriptive statistics and paired t-tests analysed the data, with a two-way repeated measures ANOVA used to compare outcomes between patients with and without diabetes. Raw and Standardized mean differences (Cohen’s d) are presented for each measure. Results The average age of participants was 57.09 years (SD = 13.66), with 40% female. Amputation types were below-knee (65.7%), above-knee (25.7%), and other (8.6%). The main causes of amputation included diabetic foot infection (25.7%), peripheral vascular disease (34.3%), trauma (25.7%), and other (14.3%). Ten participants had diabetes, and 20% had depression. Calcitonin was associated with significant reductions in pain outcomes from pre- to post-intervention (Day 0 to Day 7), with calcitonin given from day 1–3. Mean pain intensity decreased from 6.41 to 5.24 (Cohen’s d = 0.66); p = 0.02), and pain-related distress decreased from 5.85 to 4.81 (Cohen’s d = 0.71; p = 0.014). Perceived pain relief scores increased from 33.69 to 58.21, indicating greater patient-reported pain relief following treatment (Cohen’s d = 0.53; p = 0.035). No significant differences in pain intensity or distress were observed between patients with and without diabetes. Additionally, there was no significant change in the Oral Morphine Equivalent Daily Dose (p = 0.94). Conclusion In conclusion, calcitonin significantly reduced perceived pain intensity and pain-related distress scores while increasing perceived pain relief scores (i.e., patients’ reported degree of pain reduction), with similar effects observed in both patients with and without diabetes.