julilili42/papers huggingface dataset:
The course of mechanical allodynia differs between forelimb innervation territories following median nerve injury in the rat
2025-09-19

Functional deficits and chronic neuropathic pain after peripheral nerve injuries pose major clinical challenges. For preclinical evaluation of novel treatments, reliable methods for assessing functional recovery and robust animal models with high translational potential are crucial. Following peripheral nerve injury reinnervation of denervated target organs is not only achieved by regeneration of the original nerve, but also by collateral sprouting of adjacent intact nerves. In this study motor and sensory recovery was analyzed in a rat model of median nerve injury and repair using distinct functional test. Ten male Wistar rats underwent bilateral median nerve transection. In one forelimb the nerve was repaired using epineurial sutures, while in the contralateral forelimb the nerve remained unrepaired and served as internal control. For 12 weeks post-surgery, the Von Frey Test, the Grasping Test and CatWalk gait analysis were performed weekly. Sensory reinnervation and mechanical allodynia were evaluated with the Von Frey Test in distinct predefined test areas considering the innervation of the forepaws, allowing for indirect assessment of collateral nerve sprouting. Early mechanical allodynia developed within two weeks after median nerve injury in all innervation areas of the forepaw. This was associated with significant alterations of Print Width, Print Area, Duty Cycle, Swing Speed, Swing Time and Stand Index. From week 6 onward late mechanical allodynia paralleled with gait improvements and return of measurable grasping strength on the reconstructed side. The methodology utilized in our study, is feasible to comprehensively assess motor and sensory nerve regeneration paving the way for valid evaluation of future therapeutic strategies in a rat median nerve injury model.
Global consequences of long-term mineral fertilization on soil microbiomes
2025-09-19

<title>Abstract</title> Mineral fertilization has sustained food security for decades, yet its long-term impacts on soil microbial communities underpinning soil health remain virtually unknown. We combined standardized field surveys and literature synthesis to assemble a global dataset of 501 long-term agricultural experiments (median 25 years) to evaluate the impacts of sustained mineral fertilization on soil properties, microbes and functions. A biogeochemical trade-off between organic carbon accumulation and acidification was observed under long-term mineral fertilization. Microbial biomass increased with soil organic carbon accumulation, and we found major shifts in dominant soil taxa with the relative abundance of Proteobacteria increasing and that of Firmicutes declining with acidification. Virulent bacteriophages increased, with host associations consistent with these bacterial shifts. Microbial activities revealed a decoupling of increased nitrogen- and phosphorus-acquisition enzymes without effects on carbon-mineralization enzymes. Microbial communities were taxonomically reorganized without reducing richness or promoting fungal pathogens. Our findings provide global-scale evidence on the consequences of long-term mineral fertilization for soil health, which is integral to guiding fertilizer management for sustainable agriculture.
Exploratory trajectory inference reveals convergent lineages for CD8 T cells in chronic LCMV infection
2025-09-19

Trajectory inference refers to the task of reconstructing state sequences of dynamic processes from single-cell RNA sequencing (scRNAseq) data. This task frequently results in ambiguous results due to the noisiness of the data. While this issue has been alleviated by the incorporation of directional information from RNA velocity analyses, it remains difficult to resolve complex differentiation topologies, such as convergent trajectories. We introduce exploratory trajectory inference to address this challenge. This approach considers unsupervised clustering analysis of trajectory ensembles derived from simulation-based trajectory inference to deduce differentiation lineages in a data-driven fashion. We assess this approach to resolve the convergent differentiation trajectories in CD8 T-cell differentiation in chronic infections. We utilize an original scRNAseq time-series dataset of CD8 T cells collected during the time course of a chronic LCMV infection. Simulation-based trajectory inference identified a branch region early during chronic infection where cells separate into an exhausted and a memory-like lineage. Exploratory trajectory inference further allowed us to identify a convergent differentiation trajectory traversing memory-like states and ending in the exhausted population. Adoptive transfer experiments showed CD8 T cells with predicted memory-like fate differentiating into both memory-like and exhaustion states, confirming the convergent differentiation topology. We expect exploratory trajectory inference to be applicable in other scRNAseq-based studies aiming at comprehensive characterization of differentiation trajectories with bifurcating and convergent topologies.
Integrated Omics-Based Discovery of Bioactive Halogenated Metabolites from the Deep-Sea Streptomyces sp. B188M101
2025-09-19

Using the one-strain-many-compounds (OSMAC) culturing approach, metabolomic studies, and bioassay-guided purification, we have isolated and characterised three new chlorinated natural products, agelolines B-D (1–3), together with two known compounds, ageloline A (4) and gausemycin A (5), which have been identified by high-resolution mass spectrometry and 1D and 2D NMR analyses. The preliminary evaluation of three small-scale extracts (M400, R358 and SGG) against the fish pathogen, Aeromonas salmonicida subsp. achromogenes KELDUR265-87, showed that the R358 extract displayed significant activity. Furthermore, the natural products (1–5) were evaluated against the fish pathogen Aeromonas salmonicida and human pathogens (Stenotrophomonas maltophilia L2125, Staphylococcus aureus ATCC6538P, and S. pneumoniae L44) using a serial dilution assay. Compound 3 displayed activity against Staphylococcus aureus ATCC6538P, S. maltophilia L2125, and S. pneumoniae L44 with MIC values of 6, 32, and 64 μg/mL, respectively. Interestingly, only gausemycin A (5) exhibited considerable inhibition against A. salmonicida with an MIC value of 32 μg/mL, and the activity increased by two-fold when supplemented with 0.45 mM calcium salt, while 2 and 4 showed moderate inhibition against S. maltophilia L2125. The biosynthetic pathways of compounds 1–4 were proposed. This is the first report of specific inhibition of A. salmonicida by 5.
Evolutionary history and recurrent host adaptation in ancient Salmonella enterica
2025-09-20

Abstract Salmonella enterica subsp. enterica is an extremely diverse bacterial pathogen causing frequent infections and foodborne disease among human populations. More than 1500 different bacterial strains (serovars) have been described, many with a wide host range. A small number of serovars are adapted to infect specific hosts: of these, serovars Typhi and Paratyphi A, B, and C cause primate-specific systemic infections (typhoid and paratyphoid fever). Although Paratyphi C is one of the rarest human-specific serovars today, it was once widespread, and all ancient Salmonella genomes published to date belong to or are ancestral to this lineage. Here, we present 53 new ancient Salmonella genomes spanning Eurasia and dating between 3500 BCE and 1300 CE. This rich genomic dataset allows us to reconstruct the evolutionary history of this pathogen in unprecedented detail. We identify multiple extinct prehistoric lineages that caused infections throughout Eurasia. Multiple lineage replacement events are observed throughout prehistoric and historic times, and Bayesian phylogenetic analysis is used to date and identify host adaptation events within this lineage. We find that host-adapted sublineages Paratyphi C, Choleraesuis, and Typhisuis continued to evolve host specificity independently from each other. We reconstruct signals of convergent host adaptation in the studied lineages and other host-adapted strains by analysing shared pseudogenes and recurrent gene gain and loss events. This analysis demonstrates a role for host interactions as a particular target of selection, highlighting the gradual adaptation of this S. enterica lineage to humans that coincides with the intensification of animal husbandry in pastoralist and sedentary farming societies.
Repurposing passenger amplifications as Trojan horses identifies MPZL1 as a potent target for solid cancers
2025-09-20

Abstract Personalized cancer therapies focus mostly on targeting driver alterations, such as oncogenic point mutations or oncogenic driver events within large somatic copy number alterations. However, these alterations are often not actionable or only present in a small subset of patients. We hypothesized that passenger events, specifically in amplified regions, could be therapeutically exploited by providing actionable molecules on the cell surface, serving as Trojan horses for specific therapy delivery. Applying a multiomics in silico approach, we identified MPZL1 ( Myelin protein zero-like 1 ), a glycosylated cell surface receptor located on chromosome 1q, as a promising candidate, which is amplified in up to 75% of cases in several solid cancers. Notably, immunohistochemistry of a wide range of human cancer tissues (n=2244 samples) as well as normal tissues revealed strong membranous MPZL1 expression in a majority of solid tumors (e.g. 48% of hepatocellular carcinomas or 89% of triple-negative breast cancers), whereas healthy tissues were mostly negative or just faintly positive for MPZL1. Next, we generated a highly specific monoclonal antibody directed to the extracellular domain of human MPZL1 protein and utilized this antibody to produce MPZL1 CAR-T cells. MPZL1 CAR-T cells showed high specificity as well as high sensitivity in targeting a multitude of human cancer cell lines (e.g. liver, breast, and lung cancer) with high MPZL1 expression in vitro. Finally, we demonstrate strong therapeutic efficiency of MPZL1 CAR-T cells not only in different human xenograft tumors in vivo but also in a unique autochthonous liver cancer mouse model. Our work provides a framework to target passenger events within large chromosomal amplifications, reveals MPZL1 as a new trojan horse entry point for therapies of 1q-amplified cancers, and as such opens a new avenue for innovative approaches in anti-cancer drug development.
The sound of quintessence: analogue Kiselev acoustic black holes
2025-09-20

Abstract In this work, we demonstrate that the geometry of a spherically symmetric black hole surrounded by a Kiselev anisotropic fluid can be effectively mimicked by an experimental setup as the ones used to investigate some physical phenomena associated with acoustic black holes. Thus, we construct the metric describing Kiselev acoustic black holes by using the Gross–Pitaevskii theory and present a general analytical solution that encompasses, as particular cases, several classes of geometries associated with black holes. This unified framework allows for the description of a wide variety of analogue spacetimes, including new analogue geometries that have not been previously explored in the literature. Then, we examine the behavior of scalar field perturbations in this background by solving the massless Klein–Gordon equation. Depending on the boundary conditions between the acoustic event horizon and infinity, we obtain the quasinormal and quasibound spectra. This study opens up avenues for experimental investigation within the context of analog gravity models, by offering new possibilities to simulate and study black hole phenomena in laboratory settings.
More Than Just Anxiety: Math Attitudes as Key Driver of University Choice
2025-09-20

ABSTRACT Mathematics anxiety influences not only math performance but also career choices, often leading individuals to avoid math‐intensive fields in higher education. While much research has been devoted to that relation, other factors, such as general and test anxiety, neuroticism, and math‐related attitudes (e.g., math self‐concept and self‐efficacy) have received less attention, although they are related to (or potentially confounded with) math anxiety. In this study, we used latent profile analysis to examine how different profiles of (math) anxiety and attitudes influence students' choice of study programs with varying levels of math content. Our sample consisted of 837 German university students enrolled in programs with low, medium, or high math intensity. We identified seven distinct profiles characterized by different combinations of anxiety and math attitudes. These profiles varied in their distribution across study programs and in the extent to which the presence of mathematics influenced program choice. Notably, differences in study choices were associated much more with math attitudes than with math anxiety. Furthermore, gender distribution varied across profiles, with women being overrepresented in profiles marked by lower math attitudes. These findings underscore the importance of considering math attitudes alongside math anxiety when examining students' academic and career choices.
The Impact of Cooperation Under Climate Constraints: An Agent-Based Model for Exploring Paleolithic Behavioral Adaptations in the Inner Asian Mountain Corridor
2025-09-20

Abstract Modern humans dispersed throughout the entire world during the Pleistocene, completing an important part of our evolutionary history. Central Asia, one of the most challenging territories to be colonized, is characterized by continental climate and stark geographic contrasts and therefore offers an ideal context for testing hypotheses about the role of human behavior in dispersals under adverse conditions. Here, we introduce an evolutionary theoretical agent-based model exploring the effects of cooperation on dispersal under different climate constraints in two study sub-regions, the Altai and Tian Shan Mountains. The model uses an evolutionary framework to test cooperation dilemmas in four theoretical climate scenarios based on the average temperature during glacial and interglacial periods. We show that (a) population size can significantly influence the pressure on the group, such that a larger population implies more pressure to cooperate; (b) cooperative behaviors are needed for survival in the harshest conditions; and (c) if the initial probability of non-cooperation is higher, then human groups will tend to be non-cooperative even if a cooperative subgroup pushes them to cooperate. Our results demonstrate that the degree of cooperation significantly impacts survival during periods of extreme climatic deterioration. This work provides valuable insights into the mechanisms influencing the settlement of climatically challenging regions by prehistoric groups.
FLASHApp: Interactive Data Analysis and Visualization for Top‐Down Proteomics
2025-09-21

ABSTRACT Top‐down proteomics (TDP) is increasingly being applied in proteoform‐resolved biomedical and clinical research. However, the complexity of TDP data demands flexible visualization tools integrated with analysis workflows to streamline interpretation and validation. Existing tools lack adaptability and interactivity, often requiring researchers to invest considerable resources on additional manual processing and analysis to generate publication‐ready results and figures. This added layer of manual intervention impacts reproducibility, posing a significant challenge to consistent scientific outcomes. FLASHApp addresses these challenges by offering a web‐based, platform‐independent application for TDP data analysis and visualization. It integrates key tools like FLASHDeconv, featuring automated processing, interactive publication‐ready visualizations, and direct team collaboration via shareable URLs. FLASHApp is open‐source software as part of OpenMS and available at https://www.openms.org/FLASHApp/ .
Temperature-controlled transition between non-denaturing and denaturing analysis of Patisiran on a mixed-mode SAX stationary phase utilizing two-dimensional liquid chromatography
2025-09-21

Oligonucleotides are emerging nucleic acid-based therapeutics with growing clinical interest and regulatory approvals. As their use expands, reliable analytical methods are needed for quality assessment. Amongst them siRNA are short RNA duplexes which require quality control in non-dissociated form under non-denaturing conditions. Size-exclusion chromatography, anion-exchange chromatography and ion-pair reversed-phase liquid chromatography have been mainly employed for duplex siRNA analysis. In this work, we demonstrate that the (type of) stationary phase affects the melting temperature of the siRNA Patisiran. A silica-based porous mixed-mode triphenylphosphonium-based SAX stationary phase enabled the separation of antisense and sense single strands at 10 °C under non-denaturing conditions with NaCl-gradient elution. In the presence of this stationary phase, on-column melting of Patisiran siRNA duplex was observed at around 60 °C. At around 80 °C, the injection of the duplex siRNA resulted in denaturing conditions allowing single strand analysis on the same column. Interestingly, employing the same elution conditions on a nonporous hydrophilic polymer particle-based quaternary trimethylammonium-SAX column no dissociation, i.e. no melting, of the siRNA duplex occurred in the temperature range up to 80 °C. Thermodynamic analysis exhibited a distinct retention mechanism on the triphenylphosphonium-SAX and quaternary trimethylammonium-SAX columns. Under salt-free ion-pair reversed-phase LC conditions with 25 mM dibutylammonium acetate, the duplex was stable only under 20 °C, while above denaturing conditions were obtained. A heart-cutting 2D-LC approach was finally suggested for simultaneous non-denaturing and denaturing LC analysis of Patisiran in one analytical run. Non-denaturing LC on triphenylphosphonium-SAX stationary phase at 20 °C column temperature was employed as the first dimension which allowed intact duplex analysis and single strand excess analysis. A heart cut of the duplex peak was transferred via loop interface into the second dimension where the single strands were analysed under denaturing conditions on triphenylphosphonium-SAX stationary phase at 80 °C with the same mobile phase.
Perceptual-moment theories.
2025-09-22

The theory that the temporal flow of events is perceived as a succession of discrete moments has long fascinated psychologists and neuroscientists. Perceptual-moment theories generally hold that events appear successive and in temporal order only if their sensory messages arrive in different moments; otherwise, events appear simultaneous and in no temporal order. Three varieties of perceptual-moment theory assume that moments are disjunct and autonomous (autonomous-moments theory), that the arrival of a sensory message triggers a stream of disjunct moments (triggered-moments theory), or that an autonomous moment moves continuously (moving-moment theory). Previous psychophysical analyses of the moment concept did not respect the neural noise inherent to the brain by prohibiting any fluctuation in the moment duration or even in the transmission times. We present generalized models rooted in the three varieties of perceptual-moment theory, which allow the separation of latency noise and moment-duration noise under various plausible distributional assumptions. Our simulations demonstrate that only the autonomous-moments model does not produce central plateaus, which are often observed in simultaneity judgments and sometimes in temporal-order judgments. When fitting 18 perceptual-moment models to three simultaneity-judgment data sets and three temporal-order judgment data sets, the autonomous-moments model provides a worse fit compared to the triggered-moments and moving-moment models, consistently across both tasks and all plausible distributional assumptions. In conclusion, the rigorous psychophysical analysis suggests that even under relaxed assumptions, the classic autonomous-moments theory is unable to explain even the simplest temporal judgments. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
Microbial respiration - a biomineral perspective
2025-09-22

Abstract Microbial biomineralization is a key process in natural and anthropogenic environments. Certain bacteria and archaea produce cellular energy via anaerobic respiration using metals and metalloids as terminal electron acceptors, producing intra- and extracellular biominerals. This article explores the biomineralization of arsenic (As), iron (Fe), sulfur (S) and selenium (Se), in relation with microbial respiratory processes. Ferric iron (FeIII) and the oxyanions of As, S and Se are used as terminal electron acceptors by specialized bacteria and archaea, providing significant amounts of energy under anoxic and nutrient-limiting conditions. These transformations result in the formation of various types of arsenic sulfides, iron (oxyhydr)oxides and sulfides, elemental S/S0 and elemental Se/Se0 biominerals, which will be the focus of this review. Certain biominerals (e.g. S0) function as storage compounds; others, like Se0, may increase the density and the buoyancy of bacteria harboring them or are by-products of this process. Arsenic sulfides and iron (oxyhydr)oxides and sulfides appear to be by-product biominerals or have a yet unknown function. The use of these biominerals as biosignatures is an open topic and an ongoing debate. Further exploration of the reviewed biominerals is needed from both fundamental and applied viewpoints, aspects which will be covered in this review.
SAG1.3-derived Frizzled-targeting small-molecule compounds
2025-09-22

Exaggerated Wingless/Int1 (WNT)-Frizzled (FZD) signaling contributes to pathologies, including fibrosis and different forms of cancer. Thus, targeting FZDs as WNT receptors for therapeutic purposes constitutes a promising intervention if the imminent risk of unwanted side effects caused by the involvement of WNT-FZD signaling in stem cell regulation and tissue homeostasis can be controlled. Here, we derivatize SAG1.3 (SMO agonist), which acts through FZD<sub>6</sub> as a partial agonist. Screening of SAG1.3 derivatives identified compound 11 that competed with BODIPY (boron-dipyrromethene)-cyclopamine binding at different FZDs and inhibited WNT-induced FZD dynamics and β-catenin signaling in human embryonic kidney 293 (HEK293) cells. Furthermore, compound 11 blocked WNT-3A-induced LGR5 gene expression in human primary hepatocyte spheroids and reduced the viability of RNF43-mutated but not RNF43-wildtype pancreatic cancer cells. Based on our data, we suggest that compound 11 acts on FZDs to limit WNT- and WNT-surrogate-induced receptor dynamics, providing a valid proof of concept for targeting FZDs with small-molecule compounds.
Twisted tropical Hurwitz numbers for elliptic curves
2025-09-22

Hurwitz numbers enumerate branched morphisms between Riemann surfaces. For a fixed elliptic target, Hurwitz numbers are intimately related to mirror symmetry following work of Dijkgraaf. In recent work of Chapuy and Dołęga, a new variant of Hurwitz numbers with fixed genus 0 target was introduced that includes maps between non-orientable surfaces. These numbers are called b -Hurwitz numbers and are polynomials in a parameter b which measures the non-orientability of the involved maps. An interpretation in terms of factorisations of b -Hurwitz numbers for b=1 , so-called twisted Hurwitz numbers, was found in work of Burman and Fesler. In previous work, the authors derived a tropical geometry interpretation of these numbers. In this paper, we introduce a natural generalisation of twisted Hurwitz numbers with elliptic targets within the framework of symmetric groups. We derive a tropical interpretation of these invariants, relate them to Feynman integrals and derive an expression as a matrix element of an operator in the bosonic Fock space.