bluuebunny/crossref_metadata_2025 huggingface dataset:
Shared computational principles for mouse superior colliculus and primate population orientation selectivity
Authors: Kuo Austin , Gardner Justin L , Merriam Elisha P
Published: February 2025

While the mouse visual system is known to differ substantially from the primate, if the two systems share computational principles, then generalization of results across species may still be possible. One prominent difference is that orientation selectivity is found in mouse superficial superior colliculus (SC), but is not commonly observed in primate SC. Nevertheless, there may be conservation of computational principles if orientation selectivity in mouse superficial SC displays similar properties to primate visual cortex (V1), such as invariance to differences in other stimulus dimensions. However, a recent calcium (Ca2+) imaging study revealed a population map for stimulus orientation in mouse superficial SC that changed with stimulus properties such as size, shape and spatial frequency, in apparent contradistinction to the computational principles for orientation selectivity in primates. To reconcile the mouse and primate mechanisms for orientation selectivity, we constructed computational models of mouse superficial SC populations with the fixed, stimulus-invariant receptive fields classically used to describe neural receptive fields in monkey lateral geniculate nucleus (LGN) and V1. We found that simulated neural responses reproduced the patterns of stimulus-dependent orientation selectivity from the imaging data. Our models provide a parsimonious explanation for stimulus-dependent orientation selectivity consistent with well-established results from sensory neurophysiology.
Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Susceptibility in Adulthood
Authors: Cool T , Rodriguez y Baena A , Rommel M , Mattingly C , Bachinsky E , Saini S , Chattopadhyaya S , Manso Bryce A , Rajendiran S , Worthington Atesh , Poscablo D , Deguzman A , Berger-Cahn T , Boyd David F , Forsberg Camilla
Published: February 2025

Tobacco use during pregnancy has many deleterious health consequences for not only the smoking mother, but also on the unborn fetus. Children of smoking mothers are reported to have higher frequency and severity of respiratory diseases later in life; however, the mechanisms driving this increased vulnerability are not clearly understood. One potential cause of increased disease susceptibility is an altered immune system, originating in epigenetically maladaptive hematopoietic stem cells (HSCs). Here, we show that perinatal nicotine exposure (PNE) alters the establishment of HSCs and fetal-derived non-traditional tissue immune cells, with no alterations in circulating immune cell numbers. Suppression of HSCs and lung immune cells persisted for weeks after PNE had ceased. Strikingly, PNE led to increased disease susceptibility and severity upon challenge with influenza A virus in adulthood. This was associated with significant and highly selective alterations in lung immune cells, emphasizing the importance of cellular mechanisms in resilience to infections. Together, these experiments demonstrate that perinatal exposures that have deleterious consequences on hematopoietic establishment can impair immune function for life and identify the cellular mechanisms by which perinatal nicotine exposure predisposes the offspring to a weakened defense against respiratory pathogens.
µFIX – Enabling Combinations of Concurrent Optogenetics and Lock-in Amplification Fiber Photometry via Removal of Optogenetic Stimulation Crosstalk
Authors: Breakstone Maxim , Chen Spencer C. , Vadapalli Sreya , Chavez Emmanuel , Parsonnet Lauren S. , Gross Robert E. , Tescarollo Fabio , Barker David J. , Sun Hai
Published: February 2025

Simultaneous fiber photometry and optogenetics is a powerful emerging technique for precisely studying the interactions of neuronal brain networks. However, spectral overlap between photometry and optogenetic components has severely limited the application of an all-optical approach. Due to spectral overlap, light from optogenetic stimulation saturates the photosensor and occludes photometry fluorescence, which is especially problematic in physically smaller model organism brains like mice. Here, we demonstrate the Multi-Frequency Interpolation X- talk removal algorithm (MuFIX, or µFIX) for recovering crosstalk-contaminated photometry responses recorded with lock-in amplification. µFIX exploits multi-frequency lock-in amplification by modeling the remaining uncontaminated data to interpolate across crosstalk- affected segments (R2∼ 1.0); we found that this approach accurately recovers the original photometry response after demodulation (Pearson’sr∼ 1.0). When applied to crosstalk- contaminated data, µFIX recovered a photometry response closely resembling the dynamics of non-crosstalk photometry recorded simultaneously. Upon further verification using simulated and empirical data, we demonstrated that µFIX reproduces any signal that underwent simulated crosstalk contamination (r∼ 1.0). We believe adopting µFIX will enable experimental designs using simultaneous fiber photometry and optogenetics that were previously not feasible due to crosstalk.
Linear dicentric chromosomes in bacterial natural isolates reveal common constraints for replicon fusion
Authors: Sanath-Kumar Ram , Rahman Arafat , Ren Zhongqing , Reynolds Ian P. , Augusta Lauren , Fuqua Clay , Weisberg Alexandra J. , Wang Xindan
Published: February 2025

Multipartite bacterial genome organization can confer advantages including coordinated gene regulation and faster genome replication but is challenging to maintain.Agrobacterium tumefacienslineages often contain a circular chromosome (Ch1), a linear chromosome (Ch2), and multiple plasmids. We previously observed that in some stocks of the lab model strain C58, Ch1 and Ch2 were fused into a linear dicentric chromosome. Here we analyzedAgrobacteriumnatural isolates from the French Collection for Plant-Associated Bacteria (CFBP) and identified two strains with fused chromosomes. Chromosome conformation capture identified integration junctions that were different from the C58 fusion strain. Genome-wide DNA replication profiling showed both replication origins remain active. Transposon sequencing revealed that partitioning systems of both chromosome centromeres are essential. Importantly, the site-specific recombinases XerCD are required for the survival of the strains containing the fusion chromosome. Our findings show that replicon fusion occurs in natural environments and that balanced replication arm sizes and proper resolution systems enable the survival of such strains.

Importance

Most bacterial genomes are monopartite with a single, circular chromosome. But some species, likeAgrobacterium tumefaciens,carry multiple chromosomes. Emergence of multipartite genomes is often related to adaptation to specific niches including pathogenesis or symbiosis. Multipartite genomes confer certain advantages, however, maintaining this complex structure can present significant challenges. We previously reported a laboratory-propagated lineage ofA. tumefaciensstrain C58 in which the circular and linear chromosomes fused to form a single dicentric chromosome. Here we discovered two environmental isolates ofA. tumefacienscontaining fused chromosomes derived from a different route, revealing the constraints and diversification of this process. We found that balanced replication arm sizes and the repurposing of multimer resolution systems enable the survival and stable maintenance of dicentric chromosomes. These findings help us better understand how multipartite genomes function across different bacterial species and the role of genomic plasticity in bacterial genetic diversification.
Pattern-triggered immunity in blue and white seed cultivars ofPapaver somniferum
Authors: Hernandéz Orozco Jhonny Stalyn , Iakovenko Oksana , Zeiner Adam , Hronková Marie , Kubásek Jiří , Kučerová Bára , Vachová Iveta , Pop Serban , Maršík Petr , Macho Markéta , Fojtíková Pavla , Rychlá Andrea , Hejna Ondřej , Kulich Ivan , Wrzaczek Michael , Janda Martin
Published: February 2025

Papaver somniferum(poppy) is a traditional component of Central and Eastern European cuisine and an important oilseed crop in the region. The crucial thread for poppy stable yield is pathogen infection. Thus, we need to understand poppy defence mechanisms in detail. The first robust layer of plant immunity, which plays a crucial role in combat against pathogens, is pattern-triggered immunity (PTI). Here, we provide the first insights into PTI in poppy. We selected four poppy varieties used in the food industry. We investigated poppy response to various peptide elicitors acting as microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs). Flg22 induced the most robust reactive oxygen species (ROS) burst among all tested peptides. Flg22 also triggered putative mitogen-activated protein kinase (MAPK) phosphorylation and seedling growth inhibition in all tested cultivars. We identifiedPsWRKY22andPsPR2as candidate marker genes suitable for monitoring poppy PTI responses. The tested poppy cultivars have low levels of salicylic acid. Callose accumulation was triggered by wounding but not by flg22. For studying PTI in poppy, wounding is a challenge that needs to be considered as it can obscure potential PTI responses. Our findings highlight conserved aspects of poppy immunity and challenges in studying poppy PTI. The established pipeline facilitates improving our understanding of poppy immunity and has the potential for widespread application in poppy breeding and improving selection for broad-spectrum disease resistance provided by enhanced PTI.

GRAPHICAL ABSTRACT

Graphical abstract

The establishment of the methods for studying pattern-triggered immunity (PTI) inPapaver somniferumL. (poppy) was inspired by the knowledge of the model plantArabidopsis thaliana. The study showed a similarity between Arabidopsis and poppy in response to flg22 but also pointed out the obstacles for PTI analysis in poppy and the differences compared to the model plant.Created with BioRender.com.
The Effect of Arsenic on Mitochondrial Fatty Acid Metabolism via Inhibition of Carnitine Palmitoyltransferase 1B and Choline Kinase Beta in C2C12 Cells
Authors: Yu Fu-Lin , Zhang Ming-Yan , Song Gang-Wei , Ning Yang-Shan , Wu Xian , Gao Yan
Published: February 2025

Arsenic can enter the human body through environmental exposure via food, drinking water, and chemotherapy for cancer. Prolonged and excessive exposure to arsenic causes various toxic reactions, leading to diseases that significantly impact health and lifespan. Increasing evidence suggests that arsenic damages skeletal muscle tissue by reducing muscle mass and causing atrophy, thereby contributing to conditions such as respiratory and cardiovascular diseases, as well as diabetes. Fatty acid β-oxidation is the most efficient mechanism for ATP production and serves as a primary energy source for tissues, including the heart and skeletal muscles. However, the metabolic mechanisms underlying arsenic’s effects on muscle function and pathogenesis remain incompletely understood. In this study, we investigated the role of mitochondrial fatty acid oxidation in arsenic-induced muscular damage using mouse skeletal muscle C2C12 cells. Our results demonstrated a dose-dependent inhibitory effect of sodium arsenite (0-2 µM, 72 hours) on C2C12 cells proliferation, viability, and differentiation (indicated by reduction of myogenic differentiation 1 mRNA expression). Arsenic exposure disrupted mitochondria through increasing reactive oxygen species production, reducing mitochondrial membrane potential, downregulating mitochondrial fatty acid metabolism-related enzymes (carnitine palmitoyltransferase 1B and choline kinase beta mRNA), and decreasing mitochondrial DNA copy number. These findings suggest that arsenic-induced pathological changes in skeletal muscle are associated with impaired mitochondrial membrane function, disrupted fatty acid metabolism, and reduced mitochondrial DNA content in muscle cells.
De novobiosynthesis of cannabinoid and its analogs inYarrowia lipolytica
Authors: Hong Yuxiang , Gu Yang , Lin Dewei , Wu Zizhao , Chen Wenhao , Lu Tianjian , Lertphadungkit Pornpatsorn , Ma Jingbo , Wang Haili , Zhou Bo , Bar-Sela Gil , Cohen Idan , Xu Peng
Published: February 2025

Cannabis sativahas long been a cornerstone of both medicinal and cultural practices, with its therapeutic use spanning over 2,700 years. Central to its therapeutic effects are cannabinoids, which interact with the endocannabinoid system to influence various physiological processes such as anxiety, pain, and inflammation. Despite its benefits, cannabinoid production faces challenges and scarcity from plant extraction. This work leveragesYarrowia lipolyticaas a platform for cannabinoid biosynthesis. By optimizing precursor supply, engineering biomolecular condensate-like dual prenyltransferase expression and expanding endogenous metabolism with a noncanonical polyketide synthase, we achieved thede novobiosynthesis of various cannabinoid and its analogs. Our engineeredY. lipolyticaproduced ∼3.5 mg/L of cannabigerolic acid, 18.8 mg/L of orsellinic acid, and 0.5 mg/L of cannabigerorcinic acid. Additionally, CBGA titer reached 15.7 mg/L with olivetolic acid supplement. This work demonstratesY. lipolytica’s versatility as a promising host for cannabinoid and its analogs production, which opens avenues for further research and medicinal applications.
Noncommunicable diseases associated with hemorrhagic disorders, hospitalization and mortality in patients with dengue in Mexico: a national analysis of confirmed cases in 2024
Authors: Hernández Galdamez Diego Rolando , González-Block Miguel Ángel , Romo-Dueñas Daniela Karola , Osorio López Erick Antonio , Cerón-Meza Rosalba , Méndez-Hernández Pablo
Published: February 2025

Background

In Mexico, some of the most prevalent non-communicable diseases (NCDs) among adults are diabetes, hypertension, and chronic kidney disease (CKD). Mexico could be going through a syndemic of dengue and NCDs. This study aims to describe and analyze the association between the prevalence of NCDs and hospitalization, the presence of hemorrhagic disorders, and death in all officially confirmed cases of dengue in Mexico during 2024.

Methodology/Principal Findings

This cross-sectional study is carried out through a secondary analysis of the confirmed cases of dengue reported in 2024. The likelihood of hospitalization, hemorrhagic disorders, and death were assessed according to NCDs, estimating odds ratios (ORs). A multivariate logistic regression model was used, adjusting by age, sex, and for each of the NCDs (diabetes, hypertension, chronic kidney disease, immunosuppression, cirrhosis, and peptic ulcer disease). The most co-prevalent non-communicable diseases were diabetes, hypertension, CKD, and immunosuppression. For hospitalization, CKD has the highest risk of hospitalization (OR 5.73), followed by immunosuppression (OR 2.84), peptic ulcer disease (OR 2.35), and diabetes (OR 2.09). We found higher probabilities for having bleeding disorders in people with diabetes (OR 19.51), peptic ulcer disease (OR 7.85), immunosuppression (OR 4.75), cirrhosis (OR 3.37), and hypertension (OR 2.99) compared to people who did not have these diseases. The highest risk for death was observed in the cases with CKD (OR 6.54), followed by peptic ulcer disease (OR 3.09) and diabetes (OR 2.87).

Conclusions/Significance

Patients with dengue and some comorbidities were more likely to have worse clinical outcomes, such as being hospitalized, having bleeding disorders, or dying. The syndemic of NCDs and dengue in Mexico has been rapidly increasing, and this problem needs to be addressed. This work demonstrates that patients with these comorbidities have worse clinical outcomes.
Meta-analysis identifies the patient classification major impact on the ACPA association with rheumatoid arthritis-associated interstitial lung disease (RA-ILD)
Authors: Kaczmarczyk Bartosz , Conde Carmen , Gonzalez Antonio
Published: February 2025

Background

We need screening for RA patients at high risk of RA-ILD to prevent the associated decrease in life quality and survival. The proposed screenings disagree regarding the anti-citrullinated protein antibodies (ACPA) because of their inconsistent association across recent studies. Therefore, we hypothesized that meta-analysis of the published reports should reveal clues explaining the heterogeneity of results and that knowing them could help us progress in RA-ILD early detection.

Objectives

We aimed to discover the factors accounting for the variability of the ACPA association in the published reports.

Methods

We searched the Web of Science and PubMed databases for studies reporting ACPA in RA-ILD and RA-control groups. The identified studies were analyzed using meta-analysis and meta-regression to identify moderators of the ACPA association.

Results

We found 513 unique records, containing 31 eligible data sets. The meta-analysis preceding the search for moderators showed a remarkable heterogeneity (pQ= 5.7 x 10-7). Appropriate tests showed that it was largely attributable (58.1 %) to an outlier study, which had recruited cases and controls in different place and time contexts. The exclusion of this outlier from subsequent analyses did not completely remove heterogeneity (pQ= 0.004). However, it permitted the identification of the patient classification method as a significant moderator: The 14 studies using chest CT showed stronger ACPA association with RA-ILD (OR = 3.05 [95%CI: 2.12-4.38]) than the 16 employing multifactorial criteria (1.55 [95%CI: 1.18-2.03]; p = 0.0047 for the contrast). This moderator accounted for the significant heterogeneity (pQ= 0.079), was robust in sensitivity analyses, and was the only one found.

Conclusions

Our results validate the ACPA association with RA-ILD, reinforce the importance of study design, and suggest the need to consider if studies relying on chest CT for classification could be more fruitful in the search for RA-ILD biomarkers.
Does immersive VR improve diagnostic accuracy of post-stroke spatial neglect relative to conventional and digital tests?
Authors: Palmans Elise , Tuts Nora , Michiels Karla , Note Eline , Van den Bussche Eva , Gillebert Céline R. , Huygelier Hanne
Published: February 2025

Objective

Assessing post-stroke spatial neglect in immersive Virtual Reality (iVR) may improve diagnostic accuracy due to its ability to combine experimental control with increased ecological validity. This study investigated the diagnostic accuracy of an iVR assessment relative to conventional and non-iVR digital tests. Additionally, feasibility was evaluated.

Method

Stroke patients performed an iVR assessment, conventional pen-and-paper tests (3 Cancellation tests and a line bisection test), and non-iVR digital tests (Digital Cancellation and Posner test). A new Bayesian statistical method was developed to address the absence of a gold standard for neglect. Instead of conventional diagnostic cut-offs, we quantified the uncertainty of classifying patients as having neglect or not and incorporated this into estimating diagnostic accuracy. Feasibility was evaluated using recruitment and drop-out rates, sample characteristics, cybersickness and user experience.

Results

54 stroke patients and 56 healthy controls completed the study. Both iVR and non-iVR digital tests had higher diagnostic accuracies than pen-and-paper tests, although differences were not statistically significant due to high diagnostic uncertainty (resulting from inconsistencies across tests). For 6 patients, the iVR assessment and Posner test indicated neglect, while pen-and-paper tests did not. The iVR assessment was feasible for most patients, with low cybersickness and positive evaluations.

Conclusion

The iVR assessment and Posner test identified spatial biases missed by conventional tests. Inconsistencies across tests highlight the complexity of neglect assessment, suggesting that future studies should explore crucial test characteristics needed for a precise and sensitive evaluation. Furthermore, results established good feasibility of iVR neglect assessment.
Chronic Traumatic Encephalopathy Neuropathologic Change is Infrequent Following Isolated Moderate-Severe Traumatic Brain Injury
Authors: Selmanovic E. , Pruyser A. , Seifert A.C. , Delman B.N. , Thorn E.L. , Folkerth R. , Dams-O’Connor K.
Published: February 2025

Chronic traumatic encephalopathy-neuropathologic change (CTE-NC) has been primarily studied in contact sport athletes with repetitive head impacts (RHI). An association with isolated traumatic brain injury (TBI) is less clear. We systematically reviewed the autopsied cohort of Late Effects of TBI (LETBI), characterized primarily by isolated TBI but also including RHI, for features of CTE-NC. A consecutive series of 44 brains underwent comprehensive neuropathologic evaluation, exceeding recommended CTE consensus protocols. Of the 44, 6 (13.6%) (age range, 3rd-7thdecades; median, 6thdecade) had CTE-NC, forming the basis for this exploratory analysis. Ex vivo neuroimaging (in 4 of 6) highlighted traumatic and white matter microvascular lesions, facilitating histological sampling of subtle neuropathologies that might otherwise have been missed by conventional sectioning. Macroscopically, 5 had cortical (contusional) and white matter (torsional) volume loss, with septal lesions and hydrocephalus ex vacuo (i.e., structural lesions of moderate-severe TBI). Microscopically, tau-immunopositive neuronal and astrocytic pathology in a perivascular arrangement within sulcal depths met current pathognomonic criteria for CTE-NC in 5 (3 “low” and 2 “high” burden); 1 had more limited findings considered “suspicious” for CTE-NC. Five of 6 cases with any CTE-NC reported substantial exposure to RHI, through contact sport ranging over at least 16 years. One case had no known exposure to RHI: this case (death: 6th decade) had 2 isolated severe TBIs (sustained 30y and 3y prior to death). Of note, one case with “high” CTE also had Alzheimer Disease Neuropathologic Change (high stage), Lewy Body Disease (limbic), and TDP43 accumulation (“polyproteinopathy”). Aging-related tau astrogliopathy, mostly subpial, was seen in 4 cases. Glial tau was also noted around old cavitary contusions in 2. These findings converge with prior studies demonstrating that CTE is largely associated with RHI and is infrequent among individuals with isolated TBI.
A combination of phenotypic responses and genetic adaptations enablesStaphylococcus aureusto withstand inhibitory molecules secreted byPseudomonas aeruginosa
Authors: Schwyter Lukas , Niggli Selina , Zajac Natalia , Poveda Lucy , Wolski Witold Eryk , Panse Christian , Schlapbach Ralph , Kümmerli Rolf , Grossmann Jonas
Published: February 2025

Staphylococcus aureusandPseudomonas aeruginosafrequently co-occur in infections, and there is evidence that their interactions can negatively affect disease outcomes.P. aeruginosais known to be dominant, often compromisingS. aureusthrough the secretion of inhibitory compounds. We previously demonstrated thatS. aureuscan become resistant to growth-inhibitory compounds during experimental evolution. While resistance arose rapidly, the underlying mechanisms were not obvious as only a few genetic mutations were associated with resistance, while ample phenotypic changes occurred. We thus hypothesize that resistance may result from a combination of phenotypic responses and genetic adaptation. Here, we tested this hypothesis using proteomics. We first focused on an evolved strain that acquired a single mutation intcyA(encoding a transmembrane transporter unit) upon exposure toP. aeruginosasupernatant. We show that this mutation leads to a complete abolishment of transporter synthesis, which confers moderate protection against PQS and selenocystine, two toxic compounds produced byP. aeruginosa. However, this genetic effect was minor compared to the fundamental phenotypic changes observed at the proteome level when both ancestral and evolvedS. aureusstrains were exposed toP. aeruginosasupernatant. Major changes involved the downregulation of virulence factors, metabolic pathways, membrane transporters, and the upregulation of ROS scavengers and an efflux pump. Our results suggest that the observed multi-variate phenotypic response is a powerful adaptive strategy, offering instant protection against competitors in fluctuating environments and reducing the need for hard-wired genetic adaptations.

Importance

Different bacterial pathogens can co-occur in infections, where they interact with one another and influence disease severity. Previous research showed that pathogens can evolve and adapt to co-infecting species. Here, we show that evolution through genetic mutations and selection are not necessarily required to change pathogen behavior. Instead, we found that the human pathogenStaphylococcus aureusis able to plastically respond to the presence ofPseudomonas aeruginosa, a competing pathogen. Through proteomics and metabolomics, we demonstrate thatS. aureusundergoes substantial proteomic alterations in response toP. aeruginosaby down-regulating virulence factor expression, changing metabolism, and mounting protective measures against toxic compounds. Our work highlights that pathogens possess sophisticated mechanisms to respond to competitors to secure growth and survival in polymicrobial infections. We predict such plastic responses to have significant impacts on infection outcomes.
Deciphering Cell-Type and Temporal-Specific Matrisome Expression Signatures in Human Cortical Development and Neurodevelopmental Disorders via scRNA-Seq Meta-Analysis
Authors: Gim Do Hyeon , Assir Muhammad Z.K. , Fowler Paul A. , Morgan Michael D. , Berg Daniel A. , Kang Eunchai
Published: February 2025

Human cortical development is a complex process involving the proliferation, differentiation, and migration of progenitor cells, all coordinated within a dynamic extracellular matrix (ECM). ECM plays a crucial role in guiding these processes, yet its specific contributions and the implications of its dysregulation in neurodevelopmental disorders (NDDs) remain underexplored. In this study, we conducted a meta-analysis of single-cell RNA sequencing (scRNA-seq) data from 37 donors, gestational weeks (GWs) 8 to 26 across six independent studies to elucidate cell type-specific matrisome gene expression signatures and their dynamics in the developing human cortex. Our analysis identified distinct matrisome gene signatures across various cell types, with significant temporal changes during cortical development. Notably, a substantial proportion of matrisome genes are associated with NDDs, exhibiting cell type, temporal and disease specificity. These findings highlight the critical role of cell type-specific matrisome regulation in cortical development and its potential involvement in NDD pathogenesis. This study provides a comprehensive map of cell type-specific matrisome signatures in the developing human cortex and highlights the importance of ECM in both normal development and the pathogenesis of NDDs.
Widespread occurrence of botulinum and tetanus neurotoxin genes in ancient DNA
Authors: Mascarenhas Shyan , Hodgins Harold P. , Doxey Andrew C.
Published: February 2025

Background

Ancient DNA collected from archaeological specimens not only provides a window into ancient human genetic diversity but also contains a rich mixture of associated microbial DNA including potential pathogens. In recent work, we identifiedC. tetaniand tetanus neurotoxin (TeNT) genes in ancient DNA datasets collected from human archaeological specimens. However, the reasons underlying the occurrence of these toxin genes and the extent to which other toxin genes are present in ancient DNA is unclear.

Methods

Here, we performed a large-scale analysis of 6,435 ancient DNA (aDNA) sequencing datasets including human and non-human sources, searching for 49 clostridial neurotoxin types and subtypes, as well as 3 additional unrelated toxins.

Results

Our search identified a total of 105 ancient DNA datasets (1.6%) containing significant matches to one or more neurotoxin genes. Consistent with our earlier work, TeNT genes were most common, found in 50 ancient DNA datasets. In addition, we identified sequences encoding diverse botulinum neurotoxins including BoNT/C (40 samples), BoNT/D (6 samples), BoNT/B (4 samples), BoNT/E (1 sample), and theEnterococcus-associated BoNT/En (10 samples). TeNT genes were detected in a broad range of ancient samples including human and animal (horse, wild bear, chimpanzee) remains, whereas the largest diversity of toxins was detected in aDNA from Egyptian mummies. Phylogenetic and sequence analysis of the identified matches revealed close identity to modern forms of these toxins. Damage analysis revealed several toxin genes with hallmarks of ancient DNA associated damage, indicative of an ancient origin.

Conclusions

Our work reveals that clostridial neurotoxin genes occur frequently in aDNA samples, including human and animal-associated toxin variants. We conclude that the frequent association of these genes with aDNA likely reflects a strong ecological association of pathogenic clostridia with decaying human and animal remains and possible post-mortem colonization of these samples.
mTOR regulates Wnt signaling to promote tension-mediated lens vesicle closure
Authors: Wang Qian , Wu Hao , Mao Yingyu , Chow Alyssa , Bouaziz Michael , Wu Yihua , Zhang Xin
Published: February 2025

Lens vesicle closure is a pivotal event in ocular morphogenesis, and its disruption underlies Peters anomaly, a leading congenital cause of corneal opacity. Here, we elucidate a mechanistic hierarchy in which mTOR-Wnt signaling orchestrates cytoskeletal tension to drive this process. Conditional ablation of mTOR in the lens ectoderm induces aberrant corneal-lenticular stalk formation and transdifferentiation of the ciliary margin into neural retina. mTOR inhibition suppresses Wnt3 expression, and Wnt3 displayed a similar lens stalk phenotype, positioning mTOR as an upstream regulator of Wnt ligand production. Complete ablation of lens-derived Wnt ligands via deletion of the Wnt transporter Wls exacerbates developmental defects, triggering anterior lens herniation and ciliary margin development failure. Disruption of β-catenin-mediated Wnt signaling or dual deletion of Wnt co-receptors Lrp5/6 in lens ectoderm similarly prevents vesicle closure, recapitulating lens herniation. Strikingly, Rac1 deletion rescues corneal-lenticular stalk phenotypes in mTOR, Wls, and β-catenin mutants, directly linking Wnt effectors to cytoskeletal remodeling. Our findings establish an mTOR-Wnt-Rac1 signaling axis as the core regulator of cytoskeletal tension required for lens vesicle closure.
Single-nucleus multiomics of murine gonadal cells reveals transcriptional regulatory network underlying supporting lineage differentiation
Authors: Chen Yu-Ying , Rodriguez Karina , Alexander Adriana K. , Xu Xin , Papas Brian , Estermann Martin A. , Yao Humphrey Hung-Chang
Published: February 2025

Sex determination of mammalian gonads hinges upon sex-specific differentiation of gonadal supporting cells: Sertoli cells in the testis and granulosa cells in the ovary. To gain insights into how supporting cells acquire their identities, we performed joint single-nucleus transcriptomics and chromatin accessibility assays on murine gonadal cells across sex determination. By contrasting sex-specific gene expression and corresponding chromatin accessibility among progenitor and differentiated cells, we discovered that sex-specific chromatin regions in supporting cells are established shortly after sex determination, accompanied by the acquisition of active histone marks. The presence of potential transcription factor binding motifs in the open chromatin regions revealed regulatory networks underlying ovary-enriched factors LEF1 and MSX1, which promote granulosa fate by inducing granulosa-specific genes such asFoxl2andFst. Our results not only identify the gene regulatory framework underlying supporting cell sex differentiation, but also provide invaluable resources for the field.

Teaser

Sex-specific changes in chromatin and gene expression underly the divergent developmental fates of the bipotential gonadal primordium.
Cell Type-Agnostic Transcriptomic Signatures Enable Uniform Comparisons of Neurodevelopment
Authors: Venkatesan Sridevi , Werner Jonathan M. , Li Yun , Gillis Jesse
Published: February 2025

Single-cell transcriptomics has revolutionized our understanding of neurodevelopmental cell identities, yet, predicting a cell type’s developmental state from its transcriptome remains a challenge. We perform a meta-analysis of developing human brain datasets comprising over 2.8 million cells, identifying both tissue-level and cell-autonomous predictors of developmental age. While tissue composition predicts age within individual studies, it fails to generalize, whereas specific cell type proportions reliably track developmental time across datasets. Training regularized regression models to infer cell-autonomous maturation, we find that a cell type-agnostic model achieves the highest accuracy (error = 2.6 weeks), robustly capturing developmental dynamics across diverse cell types and datasets. This model generalizes to human neural organoids, accurately predicting normal developmental trajectories (R = 0.91) and disease-induced shiftsin vitro. Furthermore, it extends to the developing mouse brain, revealing an accelerated developmental tempo relative to humans. Our work provides a unified framework for comparing neurodevelopment across contexts, model systems, and species.
A network of coiled-coil and actin-like proteins controls the cellular organization of magnetosome organelles in deep-branching magnetotactic bacteria
Authors: Russell Virginia V. , Iavarone Anthony T. , Ozyamak Ertan , Grant Carly , Komeili Arash
Published: February 2025

Magnetotactic Bacteria (MTB) are a diverse group of microorganisms that use magnetosomes, organelles composed of magnetite or greigite, to navigate along geomagnetic fields. While MTB span several phyla and exhibit diverse phenotypes, magnetosome formation has been mechanistically studied in only two species ofAlphaproteobacteria. Here, we useDesulfovibrio magneticusRS-1 to uncover the mechanisms behind tooth-shaped magnetosome assembly in deep-branching MTB. Our findings reveal that RS-1 magnetic particles initially form randomly within the cell before localizing to the positive cell curvature. Genetic and proteomic analyses indicate that early biomineralization involves membrane-associated proteins found in all MTB, while later stages depend on coiled-coil (Mad20, 23, 25, and 26) and actin-like (MamK and Mad28) proteins, most of which are unique to deep-branching MTB. These findings suggest that while biomineralization originates from a common ancestor, magnetosome chain formation has diverged evolutionarily among different MTB lineages.
Fractional and Geometric Neural Dynamics: Investigating Intelligence-Related Differences in EEG Symmetry and Connectivity
Authors: Tozzi Arturo , Jaušovec Ksenija
Published: February 2025

Understanding intelligence-related variations in electroencephalographic (EEG) activity requires advanced mathematical approaches capable of capturing geometric transformations and long-range dependencies in neural dynamics. These approaches may provide methodological advantages over conventional spectral and connectivity-based techniques by offering deeper insights into the structural and functional organization of neural networks. In this study, we integrate Clifford algebra, Noether’s theorem and fractional calculus to analyze EEG signals from high- and low-IQ individuals, looking for key intelligence-related differences in cortical organization. Clifford algebra enables the representation of EEG signals as multivectors, preserving both magnitude and directional relationships across cortical regions. Noether’s theorem provides a quantitative measure of symmetry properties linked to spectral features, identifying conserved functional patterns across distinct brain regions. Mittag-Leffler functions, derived from fractional calculus, characterize long-range dependencies in neural oscillations, allowing for the detection of memory effects and scale-invariant properties often overlooked by traditional methods. We found significant differences between high- and low-IQ individuals in geometric trajectories, hemispheric connectivity, spectral properties and fractional-order dynamics. High-IQ individuals exhibited increased spectral asymmetry, enhanced spectral differentiation, distinct geometric trajectories and greater fractional connectivity, particularly in frontal and central regions. In contrast, low-IQ individuals displayed more uniform hemispheric connectivity and heightened fractional activity in occipital areas. Mittag-Leffler fractional exponents further indicated that high-IQ individuals possessed more varied neural synchronization patterns. Overall, our multi-faceted approach suggests that intelligence-related neural dynamics are characterized by an asymmetric, functionally specialized and fractionally complex cortical organization. This results in significant differences in network topology, efficiency, modularity and long-range dependencies.
Impurities in a trapped one-dimensional Bose gas of arbitrary interaction strength: Localization-delocalization transition and absence of self-localization
Authors: Breu Dennis , Vidal Marcos Eric , Will Martin , Fleischhauer Michael
Published: February 2025

We discuss impurities in a one-dimensional Bose gas with arbitrary boson-boson and boson-impurity interactions. To fully account for quantum effects, we employ numerical simulations based on the density-matrix renormalization group (DMRG) and—in the regime of strong boson-boson interactions—the mapping to weakly interacting fermions. A mean-field description of the Bose polaron based on coupled Gross–Pitaevskii Schrödinger equations predicts the existence of a self-localized polaron. We here show that such a solution does not exist and is an artifact of the underlying decoupling approximation. To this end we consider a mobile impurity in a box potential. Our work demonstrates that correlations between the impurity position and the bosons are important even in the limit where mean-field approaches are expected to work well. Furthermore, we derive analytical approximations for the energy of a single polaron formed by a heavy impurity for arbitrary interaction strengths and large but finite boson-boson couplings which accurately reproduce DMRG results. This demonstrates that the polaron problem of a heavy impurity in a one-dimensional Bose gas can be accurately approximated by a proper mean-field description plus a linearized treatment of quantum fluctuations for arbitrary boson-boson and impurity-boson couplings. Finally, we determine the polaron-polaron interaction potential V(r) in the Born-Oppenheimer approximation for small and intermediate distances r, which in the Tonks gas limit is oscillatory due to Friedel oscillations in the Bose gas.

Published by the American Physical Society
2025
Kinetic data-driven approach to turbulence subgrid modeling
Authors: Ortali G. , Gabbana A. , Demo N. , Rozza G. , Toschi F.
Published: February 2025

Numerical simulations of turbulent flows are well known to pose extreme computational challenges because of the huge number of dynamical degrees of freedom required to correctly describe the complex multiscale statistical correlations of the velocity. On the other hand, kinetic mesoscale approaches based on the Boltzmann equation, have the potential to describe a broad range of flows, stretching well beyond the special case of gases close to equilibrium, which results in the ordinary Navier-Stokes dynamics. Here, we demonstrate that, by properly tuning, a kinetic approach can statistically reproduce the quantitative dynamics of the larger scales in turbulence, thereby providing an alternative, computationally efficient and physically rooted approach toward subgrid scale (SGS) modeling in turbulence. More specifically, we show that by leveraging data from fully resolved direct numerical simulation (DNS), we can learn a collision operator for the discretized Boltzmann equation solver (the lattice Boltzmann method), which effectively implies a turbulence subgrid closure model. The mesoscopic nature of our formulation makes the learning problem fully local in both space and time, leading to reduced computational costs and enhanced generalization capabilities. We show that the model offers superior performance compared to traditional methods, such as the Smagorinsky model, being less dissipative and, therefore, able to more closely capture the intermittency of higher-order velocity correlations. This foundational study lays the basis for extending the proposed framework to different turbulent flow settings and—most importantly—to develop new classes of hybrid data-driven kinetic-based models capable of faithfully capturing the complex macroscopic dynamics of diverse physical systems such as emulsions, non-Newtonian fluid, and multiphase systems.

Published by the American Physical Society
2025
Dispersive Dark Excitons in van der Waals Ferromagnet
CrI3
Authors: He W. , Sears J. , Barantani F. , Kim T. , Villanova J. W. , Berlijn T. , Lajer M. , McGuire M. A. , Pelliciari J. , Bisogni V. , Johnston S. , Baldini E. , Mitrano M. , Dean M. P. M.
Published: February 2025

Spin-flip dark excitons are optical-dipole-forbidden quasiparticles with remarkable potential in optoelectronics, especially when they are realized within cleavable van der Waals materials. Despite this potential, dark excitons have not yet been definitively identified in ferromagnetic van der Waals materials. Here, we report two dark excitons in a model ferromagnetic material CrI3 using high-resolution resonant inelastic x-ray scattering and show that they feature narrower linewidths compared to the bright excitons previously reported in this material. These excitons are shown to have spin-flip character, to disperse as a function of momentum, and to change through the ferromagnetic transition temperature. Given the versatility of van der Waals materials, these excitons hold promise for new types of magneto-optical functionality.

Published by the American Physical Society
2025
Mechanical Tuning of Residual Stress, Memory, and Aging in Soft Glassy Materials
Authors: Edera Paolo , Bantawa Minaspi , Aime Stefano , Bonnecaze Roger T. , Cloitre Michel
Published: February 2025

Glassy materials rapidly quenched from a liquid to a solid state upon flow cessation or cooling solidify in an out-of-equilibrium configuration, trapping residual stresses and retaining the memory of the processing conditions for very long times, which compromises their physical characterization and can adversely affect processing operations. Erasing the mechanical history encoded in disordered materials constitutes a great challenge. Here, we address this problem using experiments and particle dynamic simulations for the case of colloidal glasses made of soft particles densely packed at high volume fractions. We propose a conceptual framework that connects residual stresses, directional memory, and aging of colloidal glasses to the distribution of local shear stresses in the shearing plane. The mean value of the distribution corresponds to the macroscopic stress, the skewness carries information about directional memory, and the standard deviation is related to mechanical aging. Periodically training soft particle glasses near the yield point with a sequence of stress-controlled oscillations provides a fine-tuning of the particle stress distribution. Asymmetric shear stress distributions resulting from previous flow are transformed into symmetric distributions, thereby successfully erasing residual stresses and directional memory. The same methodology is successfully applied to colloidal and polymer gels with thixotropic properties, suggesting that it is general and may be extended to other classes of disordered materials.

Published by the American Physical Society
2025
Natural Resources and Geopolitical Risk Impact on Energy Security Risk: The Role of Renewable Energy Consumption and Foreign Direct Investment
Authors: Chen Zhongyao , He Min , Ali Muhammad
Published: February 2025

Natural resources and geopolitical risks significantly impact energy security risks. The availability and accessibility of natural resources play a significant role in determining a nation's energy vulnerability. Renewable energy consumption, particularly foreign direct investment in renewable energy projects, can help mitigate these risks by diversifying energy supplies and reducing the reliance on fossil fuels. This study examines the impact of natural resources and geopolitical risk in 38 countries at risk of geopolitical conflict between 1990 and 2021 using CO2 emissions, renewable energy consumption, and foreign direct investment as controlling variables. The long‐run analysis is based on slope heterogeneity, Westerlund cointegration, Arellano–Bond dynamic panel‐data estimation, and Robust, correlated panels corrected standard errors (PCSEs). The results indicate that the energy security index is positively associated with natural resources, geopolitical risk, CO2 emissions, and renewable energy consumption. Foreign direct investment is negatively associated with the energy security index in selected geopolitical risk countries. Improving energy security requires addressing multiple policy implications. Natural resource availability, geopolitical risk mitigation, CO2 emissions reduction, and increased renewable energy consumption are key factors. However, the negative association between FDI and energy security in selected geopolitical risk countries emphasizes the importance of careful evaluation of foreign investments to ensure their compatibility with energy security objectives. By implementing appropriate policies, countries can enhance their energy security, promote sustainable development, and mitigate risks posed by geopolitical uncertainties.
Turtle Ant Resemblance in a New World Stink Bug, Preliminary Evidence for Mimicry
Authors: Serna‐Muñoz Sebastian , Novais Samuel
Published: February 2025

In mimicry, a species signals a fitness cost or benefit to a receiver by resemblance to another model species. While ants are among the most frequent models, few cases of ant mimicry are known in stink bugs (Pentatomidae). Here, using a geometric morphometric analysis, we propose that Rio nymphs might mimic Cephalotes ants.
The Adoption Problem in the Philosophy of Logic
Authors: Fairbank Viviane , Hlobil Ulf
Published: February 2025

In the philosophy of logic, the Adoption Problem is a challenge to the claim that reasoners can, in certain ways, rationally change which logic they use. The (alleged) problem is that if someone does not already infer in accordance with some fundamental logical principles (such as Universal Instantiation or Modus Ponens), then they cannot rationally begin to do so: the “adoption” of these principles is either unnecessary or impossible. In the literature, three issues have emerged as especially contentious: (1) How should we understand the argument for the Adoption Problem? What exactly is the argument's conclusion, and how is it established, if at all? (2) How could someone who thinks that the rational adoption of logic is possible respond to the Adoption Problem? (3) What are the consequences of the Adoption Problem for related issues in the philosophy of logic? In this paper, we address each question in turn. We suggest that the Adoption Problem is best understood in the form of an inconsistent quartet of theses regarding logical inference. We classify positions on logical adoption in terms of which of these theses is abandoned, and we show that such a taxonomy of positions is useful for delineating the scope and consequences of the Adoption Problem.