Browse Articles
Discover research articles across all indexed journals
Neural and computational evidence for a predictive learning account of the testing effect
Testing enhances memory more than studying. Although numerous studies have demonstrated the robustness of this classic effect, its neural and computational origin remains debated. Predictive learning is a potential mechanism behind this phenomenon: Because predictions and prediction errors (mismatch between predictions and feedback) are more likely to be generated in testing (relative to in studying), testing can benefit more from predictive learning. We shed light on the testing effect from a multilevel analysis perspective via a combination of cognitive neuroscience experiments (fMRI) and computational modeling. Behaviorally and computationally, only a model incorporating predictive learning can account for the full breadth of behavioral patterns and the robust testing effect. At the neural level, testing and prediction error both activate the canonical reward-related brain areas in the ventral striatum, insula, and midbrain. Crucially, back sorting analysis revealed that activation in the ventral striatum, insula, and midbrain can enhance declarative memory. These results provide strong and converging evidence for a predictive learning account of the testing effect.
Implications for the distributional range of the European bark beetles under future climate change
Refugees from Ukraine value job opportunities over welfare
Understanding refugees’ destination choices is key to designing appropriate policies, but little is known about this beyond correlational patterns and the effects of isolated policy changes. To derive causal evidence on how destination country characteristics affect refugees’ destination choices, we conducted a forced-choice conjoint experiment among 3,348 Ukrainian refugees across Europe. In the survey experiment, refugees repeatedly chose between two hypothetical countries that varied on eight relevant attributes. Ukrainian refugees are uniquely suited to study the relative importance of different host country attributes as they have the right to choose in which member state of the European Union they apply for temporary protection. We find that job opportunities are a much stronger driver of destination choice than social assistance. A one SD increase in average wages makes it 16.4 percentage points more likely that the country is chosen in the survey experiment, while a corresponding increase in social assistance increases the probability of the country being chosen by only 4.5 percentage points. The ease of finding a job matching one’s qualifications is valued even more than having friends or family and knowing the language of the country. We also find strong sorting in that respondents who value knowing the language and job opportunities in our survey experiments are also more likely to have settled in countries where this is the case. Conjoint experiments can be used to assess refugees’ anticipated migratory responses to proposed policy changes.
Correction: miRNA centered regulatory networks identify FN1 and miR27b as metastatic drivers in HPV negative head and neck cancer
Pervasive horizontal transfer of adeno-associated virus capsid genes
Adeno-associated viruses (AAVs) are nonpathogenic DNA viruses with potent gene delivery capabilities, making them essential tools in gene therapy and biomedical research. Despite their therapeutic importance, key aspects of AAV natural biology remain obscure, complicating efforts to explain rare AAV-associated diseases and optimize gene therapy vectors. By analyzing sequence data from virus isolates and endogenous viral elements (EVEs), I reveal a striking evolutionary pattern: While AAV sublineages, defined by the replication-associated ( rep ) gene, have broadly codiverged with host groups over millions of years, capsid ( cap ) diversity has been shaped by extensive recombination. In particular, one capsid lineage, Mammalian-wide ( M-wide ), has spread horizontally across diverse rep lineages and host taxa through multiple recombination events. Furthermore, several AAVs with M-wide capsids—including AAV-4, AAV-12, and bovine AAV (BAAV)—originate from historical adenovirus (Ad) stocks, raising the possibility that laboratory conditions contributed to capsid transfer. Distinguishing natural from laboratory-driven recombination is essential for understanding AAV ecology and its implications for gene therapy. A systematic sequencing effort in human and primate populations is needed to assess the extent of recombinant capsid acquisition, determine the impact of laboratory-driven recombination on circulating AAV diversity, and track ongoing recombination events that could affect vector safety and efficacy.
Empirical evidence for the functional benefit of intra-specific wing shape variation in a sedentary bird, the Oriental Magpie (Pica serica)
Abstract This study investigates the intraspecific variation in wingtip shape and its effects on aerodynamic forces and flight capabilities with the Oriental Magpies as a model species. Characterized by short and rounded wings, Oriental Magpies are highly sedentary and exhibit wingtip shape variations between juveniles and adults, as well as between males and females due to physiological changes during breeding. Analysis of 115 individuals revealed a significant interaction between sex and age in the location of the wingtip, with adult females exhibiting wings with backward-shifted wingtips than other sex and age categories. In order to examine the functional aspect of this pattern of variation, we conducted wind tunnel experiments and measured the aerodynamic performances of three wings by varying the position of wingtip from forward to backward. The results show that wings with backward-shifted wingtips have higher lift coefficient compared to wings with forward-shifted wingtips, especially at low free-stream velocities. Our findings suggest that wings with backward-shifted wingtips enhance maneuverability during both turning- and straight-flight conditions, particularly during slow gliding flight. We hypothesize that aerodynamic benefits of the backward-shifted wingtips are more important for adult females, who has increased body weight with center of mass shifted to rear part of the body due to fully developed reproductive organs including eggs and follicles. Our results suggest that age- and sex-dependent wingtip shape change can be fine-tuned according to intraspecific variation in the ecological requirements of the individuals.
Correction for Brill et al., Dissociation of SYNGAP1 enzymatic and structural roles: Intrinsic excitability and seizure susceptibility
Thermomechanical and physicochemical investigation of Raw clay bricks derived from Nomayo clay and palm shell powder lignocellulosic material
Abstract This study proposes an in-depth characterization of the physicochemical, thermal and mechanical properties of unfired clay bricks derived from Nomayos clay (Cameroon), with progressive additions of palm kernel shell powder bio-based material (0 to 60% by mass). The aim was to assess the influence of lignocellulosic palm kernel shell powder on the physical and mechanical properties of unfired clay bricks, with a view to proposing a sustainable, lightweight, low-cost construction solution. To this end, physical analysis revealed a significant reduction in density (22–35%) with increasing organic matter content, attributed to the lower density of palm kernel shells. Scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX) confirms a homogeneous distribution of the main elements (C, O, Mg, Fe, Si, Al, Na, K, Ti). X-ray diffraction and Fourier transform infrared spectroscopy analysis show kaolinite as the main mineral phase, with a little amount of quartz and organic functional groups in composite samples. Thermal analysis (TGA/DTA/DTG) indicates a three-stage decomposition process: moisture loss (~ 188 °C), cellulose degradation (~ 314 °C, Δm ≈ 19.17%), and kaolinite dehydroxylation (> 500 °C), with thermal stability reached above 600 °C. Mechanical tests show a progressive decrease in compressive strength from 4.64 MPa (A0%) to 0.12 MPa (A60%), inversely correlated with organic filler content. Despite the decline in mechanical performance, these bricks show potential for lightweight, ecological and low-cost construction.
Human eyelid behavior is driven by segmental neural control of the orbicularis oculi
The eyelid performs critical functions to protect the eye and preserve functional vision. These functions are driven by contraction of the orbicularis oculi (OO), which is a unique skeletal muscle with a circular geometry and diffuse innervation. It is thought that this distributed innervation may allow for differential segmental activation and contraction, but it is not currently understood how sequenced activation patterns relate to differential muscle contraction, nor how segmental contraction creates the kinematics that drive the eyelid’s critical functions. In fact, motion of the eyelid has predominantly been modeled in only a single dimension (open–close). Here, we show that eyelid motion has important two-dimensional features that vary between eyelid behaviors. Using distributed intramuscular electromyography, we further show that activation differs segmentally across the OO, and that patterns of activation change to produce different behavior-specific eyelid kinematics. Our results demonstrate the role of segmental activation in eyelid motion, highlighting the importance of precise neural control in producing natural eyelid behavior. We anticipate that this research is a starting point for robust mechanistic models of eyelid function. This knowledge has critical implications for diagnosis and treatment of eyelid paralysis.
Comparison of microcurrent and low level laser therapy on matrix metalloproteinases and tissue inhibitors of metalloproteinases expressions in surgical wound healing
Abstract Purpose The purpose of this study was to compare the modulation effects of Microcurrent Therapy (MT) and Low-Level Laser Therapy (LLLT) on Matrix Metalloproteinases (MMPs) and tissue inhibitors of Metalloproteinases (TIMPs) expressions during healing of surgical wounds using appendectomy wound as a model. Methods Ninety patients who recently underwent appendectomy were randomly divided into 3 main groups of equal numbers. All cases in the three groups received ordinary medical therapy. Moreover, group A (MT group) received Microcurrent Therapy for 20 min. In addition to a designed physical therapy treatment protocol for 20 min. Group B (LLLT group) received Low-Level Laser Therapy for 20 min., plus the same designed physical therapy treatment protocol for 20 min. Group C (placebo group) received placebo shame LLLT for 20 min. plus the same designed physical therapy treatment protocol for 20 min. Enzyme-linked immunosorbent assay (ELISA) and Western Blot Technique (WBT) were used to determine expression levels of MMP-8, MMP-9, and TIMP-1 at the beginning of treatment and after the end of twelve successive sessions. Results Following therapies, results showed a statistically significant decrease in the MMP-8 and MMP-9 expressions with significantly increased expression levels of TIMP-1 in each group separately (P < 0.05). These changes in the expression levels towards proper healing of surgical wounds were more obvious in MT and LLLT groups compared to the placebo group, with significantly better effect in the LLLT group compared to the MT group . Conclusion Microcurrent therapy and low-level laser therapy have a notable impact in improving wound healing process as they can significantly affect the expression levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases towards good prognosis of healing process and decreasing possible wound healing complication, with superior effect of low-level laser therapy.
Tracing SARS-CoV-2 clusters across local scales using genomic data
A quantitative understanding of local transmission dynamics is essential for designing effective prevention strategies. In this study, we developed a computational workflow to identify viral introductions and trace locally circulating clusters. We analyzed over 26,000 SARS-CoV-2 genomes and their associated metadata, collected between January and October 2021, to explore introduction and local dispersal patterns in Greater Houston, a major metropolitan area known for its demographic diversity. Our analysis identified more than 1,000 independent introduction events, resulting in clusters of varying sizes. The majority of introductions originated from domestic sources, while international introductions occurred earlier and were associated with larger cluster sizes. An analysis of locally circulating clusters revealed age-structured transmission dynamics. Geographic reconstruction of cluster spread identified Harris County as the primary viral source for surrounding areas. The outbreak in the source population was characterized by 1) a smaller proportion of new cases associated with external viral imports and 2) longer persistence times of circulating lineages. Overall, our high-resolution spatiotemporal reconstruction of the epidemic provides essential insights into the local-scale transmission landscape, supporting outbreak-specific, regional response strategies and public health planning.
Adjusted imbalance ratio leads to effective AI-based drug discovery against infectious disease
Abstract The success of AI-based pipelines in Drug Discovery (DD) heavily depends on three components: the dataset (size, content, imbalance ratio), the encoding system and the predictive model. This study focuses on optimizing these elements to develop robust predictive models for the biological activity of chemical molecules. We trained five machine learning and six deep learning algorithms to predict the anti-pathogen activity of chemical compounds, derived from PubChem Bioassays targeting four infectious diseases. The datasets exhibited a significant imbalance towards the inactive class. To address this, we implemented a K-ratio random undersampling approach (K-RUS) to determine optimal imbalance ratios (IRs), and compared them to conventional resampling approaches. Across all simulations, a moderate IR (1:10) significantly enhanced models’ performance. Through external validation, we assessed the generalization power of the top-performing models and observed optimal balance between true positive and false positive rates with the 10-RUS configuration. Furthermore, we investigated the chemical similarity between active and inactive classes, which revealed the underlying mechanisms of misclassification. Our findings emphasized the need for optimizing imbalance ratios and leveraging chemical diversity to improve AI-driven DD against infectious diseases.
Tuning Fermi liquids with polaritonic cavities
The question of whether or not passive subwavelength cavities can alter the properties of quantum materials is currently attracting a great deal of attention. In this article, we show that the Fermi liquid parameters of a two-dimensional metal are modified by cavity polariton modes, and that these changes can be monitored by measuring a paradigmatic magneto-transport phenomenon, Shubnikov–de Haas oscillations in a weak perpendicular magnetic field. This effect is intrinsic, and totally unrelated to disorder. As an illustrative example, we carry out explicit calculations of the quasiparticle velocity of graphene in a planar van der Waals cavity formed by natural hyperbolic crystals and metal gates. The largest effects of the cavity occur when the phonon polariton modes of the former match energetically the graphene plasmon. For typical graphene carrier densities this occurs in the Terahertz spectral range.
Exploration and analysis of risk factors for coronary artery disease with type 2 diabetes based on SHAP explainable machine learning algorithm
O-GlcNAc modulation of nuclear pore complexes orchestrates mRNA export efficiency
Efficient gene expression depends on the tightly regulated export of messenger RNA (mRNA) through nuclear pore complexes (NPCs), which are densely modified by O-linked N-acetylglucosamine (O-GlcNAc). Although dysregulated O-GlcNAcylation has been linked to a variety of human diseases, the precise distribution of O-GlcNAc within the NPC and its effects on mRNA export remain poorly understood. Here, we combined single-point edge-excitation subdiffraction (SPEED) microscopy with stochastic optical reconstruction microscopy (STORM) to map the nanometer-scale distribution of an O-GlcNAc analog (GlcNAz) within NPCs and to quantify the export kinetics of mRNA–protein complexes (mRNPs) under both normal and perturbed O-GlcNAcylation conditions. Under basal conditions, GlcNAz is predominantly localized around the central channel of the NPC. However, both hypo- and hyper-O-GlcNAcylation cause GlcNAz to redistribute toward the nuclear and cytoplasmic peripheries. This shift is paralleled by changes in mRNP localization and altered distributions of key, highly O-GlcNAcylated, phenylalanine-glycine nucleoporins. These architectural rearrangements are accompanied by functional consequences: Elevated O-GlcNAcylation nearly doubles mRNA export efficiency (~61%), while reduced O-GlcNAcylation lowers it to ~16%, along with reduced NPC engagement. The transport receptor TAP exhibits analogous efficiency changes, reinforcing the role of O-GlcNAcylation as a key regulator of nucleocytoplasmic transport. Together, these results suggest that O-GlcNAcylation modulates NPC architecture and transport dynamics to fine-tune mRNA export, and indicate that targeted modulation of NPC O-GlcNAc levels may offer a promising strategy for addressing diseases associated with nuclear transport dysfunction.
Perceived service quality mediates the effect of physical servicescape on tourists’ intention to stay in rural homestays
CRISPR–Cas9 screening reveals microproteins regulating adipocyte proliferation and lipid metabolism
Small open reading frames (smORFs) encode microproteins that play crucial roles in various biological processes, yet their functions in adipocyte biology remain largely unexplored. In a previous study, we identified thousands of smORFs in white and brown adipocytes derived from the stromal vascular fraction of mice using ribosome profiling. Here, we expand on this work by identifying additional smORFs related to adipocytes using the in vitro 3T3-L1 preadipocyte model. To systematically investigate the functional relevance of these smORFs, we designed a custom CRISPR/Cas9 single guide RNA (sgRNA) library and screened for smORFs influencing adipocyte proliferation and differentiation. Through a dropout screen and fluorescence-assisted cell sorting of lipid droplets, we identified dozens of smORFs that regulate either cell proliferation or lipid accumulation. The smORFs on the 5’- and 3’-untranslated regions (i.e., upstream smORFs (uORFs) and downstream smORFs (dORFs)) of functional genes can exert activity through cis-regulatory effects of the main ORF on these messenger RNAs (mRNAs), such as uORFs of MDM2 that impact proliferation. However, other smORFs, especially those from mRNAs with no other ORFs, point to a functional microprotein. Indeed, we tested a candidate smORF 1183 from a long noncoding RNA 923011K14Rik and demonstrated that the microprotein regulates adipocyte differentiation. These findings highlight the potential of CRISPR/Cas9-based screening to uncover functional smORFs and provide a framework for further exploration of microproteins in adipocyte biology and metabolic regulation.
Quantum-inspired robust optimization for coordinated scheduling of PV-hydrogen microgrids under multi-dimensional uncertainties
Cryosectioning-enhanced super-resolution microscopy for single-protein imaging across cells and tissues
DNA-points accumulation for imaging in nanoscale topography (DNA-PAINT) enables nanoscale imaging with virtually unlimited multiplexing and molecular counting. Here, we address challenges, such as variable imaging performance and target accessibility, that can limit its broader applicability. Specifically, we enhance its capacity for robust single-protein imaging and molecular counting by optimizing the integration of total internal reflection fluorescence microscopy with physical sectioning, in particular, Tokuyasu cryosectioning. Our method, tomographic and kinetically enhanced DNA-PAINT (tkPAINT), achieves 3 nm localization precision across diverse samples, enhanced imager binding, and improved cellular integrity. tkPAINT can facilitate molecular counting with DNA-PAINT inside the nucleus, as demonstrated through its quantification of the in situ abundance of RNA Polymerase II in both HeLa cells as well as mouse tissues. Anticipating that tkPAINT could become a versatile tool for the exploration of biomolecular organization and interactions across cells and tissues, we also demonstrate its capacity to support multiplexing, multimodal targeting of proteins and nucleic acids, and three-dimensional (3D) imaging.