Systems Biology

Synthetic data distillation enables the extraction of clinical information at scale

Sat, 2025-05-10 06:00

NPJ Digit Med. 2025 May 10;8(1):267. doi: 10.1038/s41746-025-01681-4.

ABSTRACT

Large-language models (LLMs) show promise for clinical note information extraction, but deployment challenges include high computational costs and privacy concerns. We used synthetic data distillation to fine-tune smaller, open-source LLMs to achieve performance comparable to larger models while enabling local hardware deployment or reduced cloud costs. Using Llama-3.1-70B-Instruct, we generated synthetic question-answer training pairs to fine-tune smaller Llama models. We evaluated performance across three tasks: synthetic clinical trial criteria, the i2b2 2018 Clinical Trial Eligibility Challenge, and apixaban trial criteria questions. The 8B-parameter model achieved high accuracy across all tasks and sometimes outperformed the 70B-Instruct teacher model. Fine-tuning with only the most challenging questions still improved performance, demonstrating the value of targeted training. Results from 3B- and 1B-parameter models showed a clear size-performance tradeoff. This work demonstrates synthetic data distillation's potential for enabling scalable clinical information extraction.

PMID:40348936 | DOI:10.1038/s41746-025-01681-4

Categories: Literature Watch

Pose estimation and tracking dataset for multi-animal behavior analysis on the China Space Station

Sat, 2025-05-10 06:00

Sci Data. 2025 May 10;12(1):766. doi: 10.1038/s41597-025-05111-8.

ABSTRACT

Non-contact behavioral study through intelligent image analysis is becoming increasingly vital in animal neuroscience and ethology. The shift from traditional "black box" methods to more open and intelligent approaches is driven by advances in deep learning-based pose estimation and tracking. These technologies enable the extraction of key points and their temporal relationships from sequence images. Such approach is particularly crucial for investigating animal behaviors in outer space, with microgravity, high radiation, and hypomagnetic field. However, the limited image data of space animal and the lack of publicly accessible datasets with ground truth annotations have hindered the development of effective evaluation tools and methods. To address this challenge, we present the SpaceAnimal Dataset-the first multi-task, expert-validated dataset for multi-animal behavior analysis in complex scenarios, including model organisms such as Caenorhabditis elegans, Drosophila, and zebrafish. Additionally, this paper provides evaluation code for deep learning models, establishing benchmarks to guide future research. This dataset will advance AI technology innovation in this field, contributing to the discovery of new behavior patterns in space animals.

PMID:40348756 | DOI:10.1038/s41597-025-05111-8

Categories: Literature Watch

An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ

Sat, 2025-05-10 06:00

NPJ Parkinsons Dis. 2025 May 10;11(1):122. doi: 10.1038/s41531-025-00966-5.

ABSTRACT

Amyloid aggregation is associated with neurodegenerative disease and its modulation is a focus of drug development. We developed a chemical proteomics pipeline to probe the mechanism of action of anti-amyloidogenic compounds. Our approach identifies putative interaction sites with high resolution, can probe compound interactions with specific target conformations and directly in cell and brain extracts, and identifies off-targets. We analysed interactions of six anti-amyloidogenic compounds and the amyloid binder Thioflavin T with different conformations of the Parkinson's disease protein α-Synuclein and tested specific compounds in cell or brain lysates. AC Immune compound 2 interacted with α-Synuclein in vitro, in intact neurons and in neuronal lysates, reduced neuronal α-Synuclein levels in a seeded model, and had protective effects. EGCG, Baicalein, ThT and doxycycline interacted with α-Synuclein in vitro but not substantially in cell lysates, with many additional putative targets, underscoring the importance of testing compounds in situ. Our pipeline will enable screening of compounds against any amyloidogenic proteins in cell and patient brain extracts and mechanistic studies of compound action.

PMID:40348747 | DOI:10.1038/s41531-025-00966-5

Categories: Literature Watch

The effect of psychedelic microdosing on animal behavior: a review with recommendations for the field

Sat, 2025-05-10 06:00

Neurosci Biobehav Rev. 2025 May 8:106204. doi: 10.1016/j.neubiorev.2025.106204. Online ahead of print.

ABSTRACT

Microdosing, the repeated use of psychedelic substances at low doses, is growing in popularity among recreational consumers. While this practice is associated with many benefits to mood, well-being and health, research in this area is in its early stages and predominantly centered on human applications. In this narrative review, we synthesize the findings from studies investigating the effects of microdosing on the behaviors of three animal species: rats, mice, and zebrafish. A total of 12 studies were identified that implemented a microdosing regimen of LSD, psilocybin, or DMT in these animal models. Overall, microdosing caused little changes in behaviors associated with anxiety- and depressive-like states. Moreover, while microdosing was well-tolerated across species, further research is needed to capture specific safety concerns. Finally, we critically appraise the studies included in this review based on their methodologies and discuss further avenues of research to advance the preclinical literature on psychedelic microdosing. Specifically, we recommend that future research prioritize the replication of existing findings to inform the development of robust study designs and dosing protocols, as well as establish standardized methodologies to enable effective comparisons across different animal models. Furthermore, future investigations should explore the therapeutic potential of mescaline microdosing, examine sex-dependent effects, and extend research to additional models of psychiatric conditions, including those related to obsessive-compulsive disorder and post-traumatic stress disorder.

PMID:40348309 | DOI:10.1016/j.neubiorev.2025.106204

Categories: Literature Watch

Sla2 is a core interaction hub for clathrin light chain and the Pan1/End3/Sla1 complex

Sat, 2025-05-10 06:00

Structure. 2025 Apr 28:S0969-2126(25)00147-9. doi: 10.1016/j.str.2025.04.013. Online ahead of print.

ABSTRACT

The interaction network of Sla2, a vital endocytic mid-coat adaptor protein, undergoes constant rearrangement. Sla2 serves as a scaffold linking the membrane to the actin cytoskeleton, with its role modulated by the clathrin light chain (CLC), which inhibits Sla2's function under certain conditions. We show that Sla2 has two independent binding sites for CLC: one previously described in homologs of fungi (Sla2) and metazoa (Hip1R), and a second found only in Fungi. We present the structural model of the Sla2 actin-binding domains in the context of regulatory structural domains by cryoelectron microscopy. We provide an interaction map of Sla2 and the regulatory proteins Sla1 and Pan1, predicted by AI modeling and confirmed by molecular biophysics techniques. Pan1 may compete with CLC for the conserved Sla2-binding site. These results enhance the mapping of crucial interactions at endocytic checkpoints and highlight the divergence between Metazoa and Fungi in this vital process.

PMID:40347949 | DOI:10.1016/j.str.2025.04.013

Categories: Literature Watch

Phylogeographic and genetic network assessment of COVID-19 mitigation protocols on SARS-CoV-2 transmission in university campus residences

Sat, 2025-05-10 06:00

EBioMedicine. 2025 May 9;116:105729. doi: 10.1016/j.ebiom.2025.105729. Online ahead of print.

ABSTRACT

BACKGROUND: Congregate living provides an ideal setting for SARS-CoV-2 transmission in which many outbreaks and superspreading events occurred. To avoid large outbreaks, universities turned to remote operations during the initial COVID-19 pandemic waves in 2020 and 2021. In late-2021, the University of California San Diego (UC San Diego) facilitated the return of students to campus with comprehensive testing, vaccination, masking, wastewater surveillance, and isolation policies.

METHODS: We performed molecular epidemiological and phylogeographic analysis of 4418 SARS-CoV-2 genomes sampled from UC San Diego students during the Omicron waves between December 2021 and September 2022, representing 58% of students with confirmed SARS-CoV-2 infection. We overlaid these analyses across on-campus residential information to assess the spread and persistence of SARS-CoV-2 within university residences.

FINDINGS: Within campus residences, SARS-CoV-2 transmission was frequent among students residing in the same room or suite. However, a quarter of pairs of suitemates with concurrent infections had distantly related viruses, suggesting separate sources of infection during periods of high incidence in the surrounding community. Students with concurrent infections residing in the same building were not at substantial increased probability of being members of the same transmission cluster. Genetic network and phylogeographic inference indicated that only between 3.1 and 12.4% of infections among students could be associated with transmission within buildings outside of individual suites. The only super-spreading event we detected was related to a large event outside campus residences.

INTERPRETATION: We found little evidence for sustained SARS-CoV-2 transmission within individual buildings, aside from students who resided in the same suite. Even in the face of heightened community transmission during the 2021-2022 Omicron waves, congregate living did not result in a heightened risk for SARS-CoV-2 transmission in the context of the multi-pronged mitigation strategy.

FUNDING: SEARCH Alliance: Centers for Disease Control and Prevention (CDC) BAA (75D301-22-R-72097) and the Google Cloud Platform Research Credits Program. J.O.W.: NIH-NIAID (R01 AI135992). T.I.V.: Branco Weiss Fellowship and Newkirk Fellowship. L.L.: University of California San Diego.

PMID:40347833 | DOI:10.1016/j.ebiom.2025.105729

Categories: Literature Watch

Engineering Gypsophila elegans hairy root cultures to produce endosomal escape-enhancing saponins

Sat, 2025-05-10 06:00

Plant Biotechnol J. 2025 May 10. doi: 10.1111/pbi.70122. Online ahead of print.

ABSTRACT

The limited cytosolic delivery of DNA and protein-based therapeutics due to endosomal entrapment reduces drug efficacy, increasing treatment costs and possible side effects in human and veterinary medicine as a consequence of higher administered dosages. Plant-derived triterpenoid saponins, specifically those with endosomal escape-enhancing (EEE) properties, have shown promise in overcoming this limitation by disrupting endosomal membranes. QS-21, a well-known EEE saponin, has been used as an adjuvant in vaccines, and recent studies have elucidated its biosynthetic pathway. However, EEE saponins are typically present as minor compounds in plants, posing challenges for their large-scale production and purification. Here we investigated the possibility of engineering SO1861 production, an EEE saponin from Saponaria officinalis, using heterologous gene expression in Gypsophila elegans hairy roots, a plant species known to synthesize structurally related saponins. Via S. officinalis transcriptomics, we identified jasmonate-responsive saponin biosynthetic genes, and three cytochrome P450s (CYP450s) involved in C23, C28 and C16 oxidations were characterised. Heterologous expression of these CYP450s in G. elegans hairy roots successfully altered the saponin profile, with notable increases in SO1861 precursors in lines expressing the C23-oxidases SoCYP72A984 and SoCYP72A1003. Interestingly, expression of only SoCYP72A1003, a non-canonical C23 oxidase, resulted in the accumulation of a compound matching the SO1861 standard, suggesting the activation of a potentially latent pathway and of silent enzymes in a novel combination. This work underscores the potential of engineering strategies in heterologous plant systems to steer triterpenoid saponin biosynthetic pathways and suggests new avenues for producing high-value EEE saponins.

PMID:40347514 | DOI:10.1111/pbi.70122

Categories: Literature Watch

Protocol to identify regulatory modules in Parkinson's disease progression using miRNA data and Boolean modeling

Sat, 2025-05-10 06:00

STAR Protoc. 2025 May 8;6(2):103769. doi: 10.1016/j.xpro.2025.103769. Online ahead of print.

ABSTRACT

Regulatory modules are molecules that interact functionally, driving disease processes. Here, we present a protocol for identifying regulatory modules in Parkinson's disease (PD) using cohort-specific microRNA (miRNA) data and Boolean modeling. We describe steps for omics data collection, biomolecule and miRNA target analysis, and Boolean model construction and simulation. We then detail procedures for validation of the model and results. The modules identified using this protocol explain how miRNA-driven mechanisms influence PD progression in disease cohorts. For complete details on the use and execution of this protocol, please refer to Hemedan et al.1.

PMID:40347476 | DOI:10.1016/j.xpro.2025.103769

Categories: Literature Watch

Single intracerebroventricular TNFR2 agonist injection impacts remyelination in the cuprizone model

Sat, 2025-05-10 06:00

J Mol Med (Berl). 2025 May 10. doi: 10.1007/s00109-025-02549-6. Online ahead of print.

ABSTRACT

The development of therapeutics that enhances the regeneration of myelin sheaths following demyelination is predicted to prevent neurodegeneration. A promising target to enhance remyelination is the immunomodulatory cytokine tumor necrosis factor alpha (TNFα) and its receptors TNFR1 and TNFR2. TNFR2 on oligodendrocyte lineage cells and microglia coordinates different protective functions, such as proliferation of oligodendrocyte progenitor cells, survival of mature oligodendrocytes, and release of anti-inflammatory cytokines, in animal models of inflammation and demyelination. Here, we find in the cuprizone model that following demyelination, fewer axons are unmyelinated in the corpus callosum at an early stage of remyelination after single TNFR2 agonist delivery in the lateral ventricle, while astrocyte and microglia number and coverage are unchanged. Towards later stages of remyelination, TNFR2 agonist treatment maintains the number of oligodendrocyte lineage cells, and large caliber axons have thinner myelin. Hence, even short-term stimulation of TNFR2 has a positive impact on the remyelination processes. This study informs further on the beneficial implications of TNFR2 signaling on oligodendrocyte lineage cells and remyelination, emphasizing its potential therapeutic value for demyelinating diseases, including multiple sclerosis. KEY MESSAGES: Single TNFR2 agonist treatment in the lateral ventricle following cuprizone-induced demyelination impacts remyelination by: Leading to a lower percentage of unmyelinated axons at early stages. Preserving the number of oligodendrocyte lineage cells in the corpus callosum at later stages. Covering large calibre axons with thinner myelin sheaths at later stages.

PMID:40347238 | DOI:10.1007/s00109-025-02549-6

Categories: Literature Watch

Rewiring Estrogen Receptor α into Bisphenol Selective Receptors Using Darwin Assembly-Based Directed Evolution (DADE) in <em>Saccharomyces cerevisiae</em>

Sat, 2025-05-10 06:00

ACS Synth Biol. 2025 May 10. doi: 10.1021/acssynbio.5c00163. Online ahead of print.

ABSTRACT

Bisphenols are widely used in manufacturing plastics and resins, but their environmental persistence raises concerns to human health and ecosystems. Accurate measurements for bisphenols are crucial for effective monitoring and regulation. Analytical methods detect only preselected bisphenols, while bioassays assessing estrogen receptor α activation suffer from poor sensitivity and strong background signals due to estrogenic contaminations. To develop a bioassay in Saccharomyces cerevisiae with increased sensitivity and specificity for bisphenols, we performed multi-site directed mutagenesis and directed evolution of more than 108 stably integrated estrogen receptor variants. By mutating the estrogen receptor α towards recognition of bisphenol A in yeast, we determined the preBASE variant (M421G_V422G_V533D_L536G_Y537S) with elevated bisphenol A sensitivity (EC50:329 nM) and lost estrogen responsiveness (EC50:0,17 mM). Further engineering yielded an off-target mutant, identified as the Bisphenol-Affinity and Specificity-Enhanced (BASE) variant (M421G_V422G_V533D_L536G_Y537S_L544I) that uses bisphenols as its primary agonist (EC50:32 mM) and impaired estrogen sensitivity (EC50:85M). The rewiring into a bisphenol receptor was confirmed in ligand binding assays to purified ligand binding domains. Taken together, the identified variants form stepping stones for further protein engineering to generate bisphenol specific high-throughput yeast-based bioassays.

PMID:40347189 | DOI:10.1021/acssynbio.5c00163

Categories: Literature Watch

Global Burden of Lip and Oral Cavity Cancer From 1990 to 2021 and Projection to 2040: Findings From the 2021 Global Burden of Disease Study

Sat, 2025-05-10 06:00

Cancer Med. 2025 May;14(9):e70957. doi: 10.1002/cam4.70957.

ABSTRACT

BACKGROUND: The aim of this study was to estimate the global burden of lip and oral cavity cancer (LOC) and its trends in different genders, age groups, regions, and countries globally.

METHODS: Data were sourced from the Global Burden of Disease 2021 study.

RESULTS: During the 32-year period, a 92.92% and 113.94% increase was estimated in the absolute counts of LOC deaths and disability-adjusted life years (DALYs), respectively. Throughout the 32-year period, males exhibited higher age-standardized rates (ASRs) of incidence (ASIRs), prevalence (ASPRs), mortality (ASMRs), and DALYs (ASDRs) related to LOC. The age group of 60-64 years consistently recorded the highest numbers of new and prevalent cases across the years 1990, 2019, and 2021. In 2019 and 2021, the highest ASMR and ASDR were observed in individuals aged 95 years and older. Regions with low-middle and low socio-demographic index (SDI) consistently showed higher ASMRs and ASDRs associated with LOC from 1990 to 2021. Eastern Europe, South, North, and Southeast Asia exhibited a concentration of countries with higher ASIRs, ASPRs, ASMRs, and ASDRs in 2021. South Asia maintained high levels of ASIRs, ASPRs, ASMRs, and ASDRs in 2021. In 2021, Palau recorded the highest ASIR, ASPR, ASMR, and ASDR, followed by Pakistan. Projections indicate that ASIR, ASPR, ASMR, and ASDR are expected to increase by 7.40%, 10.10%, 2.85%, and 4.60%, respectively, from 2021 to 2040.

CONCLUSION: LOC remains a critical public health concern that requires immediate attention, particularly among certain demographics such as males, aged 60-64 or 95 and older, as well as in low- and middle-SDI regions, particularly Eastern Europe, South Asia (notably Pakistan), North Asia, and Southeast Asia.

PMID:40347073 | DOI:10.1002/cam4.70957

Categories: Literature Watch

The complexity of G protein-coupled receptor (GPCR) modulation and signalling

Sat, 2025-05-10 06:00

Br J Pharmacol. 2025 May 9. doi: 10.1111/bph.70067. Online ahead of print.

NO ABSTRACT

PMID:40347038 | DOI:10.1111/bph.70067

Categories: Literature Watch

RETRACTION: Prediction of Potential Targets and Toxicological Insights of Astragalus in Liver Cancer Based on Network Pharmacology: Integrating Systems Biology, Drug Interaction Networks, and Toxicological Perspectives

Sat, 2025-05-10 06:00

Environ Toxicol. 2025 May 10. doi: 10.1002/tox.24533. Online ahead of print.

ABSTRACT

M. Zou, Z. Zheng, Z. Xiahou, and J. Cao, "Prediction of Potential Targets and Toxicological Insights of Astragalus in Liver Cancer Based on Network Pharmacology: Integrating Systems Biology, Drug Interaction Networks, and Toxicological Perspectives," Environmental Toxicology (EarlyView): https://doi.org/10.1002/tox.24189. The above article, published online on 13 March 2024 in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, April Rodd; and Wiley Periodicals LLC. Following an investigation by the publisher, the parties have concluded that this article was accepted solely on the basis of a compromised peer review process. Therefore, the article must be retracted. The authors were notified of this decision but did not respond.

PMID:40347009 | DOI:10.1002/tox.24533

Categories: Literature Watch

Peroxiredoxin Tsa1 Regulates the Activity of Trehalose Metabolism-Related Enzymes During Wine Yeast Biomass Propagation

Sat, 2025-05-10 06:00

Microb Biotechnol. 2025 May;18(5):e70154. doi: 10.1111/1751-7915.70154.

ABSTRACT

Trehalose metabolism plays a crucial role in yeast stress tolerance during biomass propagation and dehydration, but its regulatory mechanisms under these industrial conditions remain incompletely understood. This study analyses the role of an antioxidant enzyme, the cytosolic peroxiredoxin Tsa1, in modulating trehalose metabolism in Saccharomyces cerevisiae wine strains during biomass production in molasses. Through comparative analyses in three commercial genetic backgrounds (L2056, T73, EC1118), we demonstrate that TSA1 deletion generally leads to increased intracellular trehalose accumulation despite phenotypic variability among strains. Enzymatic assays revealed that Tsa1 does not regulate trehalose synthesis by altering glycolytic/gluconeogenic flux through pyruvate kinase. However, the deletion of TSA1 resulted in increased oxidation of trehalose synthesis enzymes, as well as enhanced activity of trehalose-6-phosphate synthase and the trehalases Nth1 and Ath1, suggesting the involvement of peroxiredoxin in the futile cycle of trehalose synthesis and degradation. Scaling up the yeast biomass propagation process to semi-industrial conditions confirmed these findings, with increased trehalose levels in the tsa1∆ mutant correlating with enhanced desiccation resistance of the resulting biomass. These results highlight a novel Tsa1-dependent regulatory mechanism governing trehalose metabolism beyond its canonical antioxidant role. Understanding this pathway provides new insights into optimising yeast biomass propagation for industrial applications.

PMID:40346935 | DOI:10.1111/1751-7915.70154

Categories: Literature Watch

Positive selection and relaxed purifying selection contribute to rapid evolution of sex-biased genes in green seaweed Ulva

Fri, 2025-05-09 06:00

BMC Ecol Evol. 2025 May 9;25(1):44. doi: 10.1186/s12862-025-02382-y.

ABSTRACT

BACKGROUND: The evolution of differences in gamete size and number between sexes is a cornerstone of sexual selection theories. The green macroalga Ulva, with incipient anisogamy and parthenogenetic gametes, provides a unique system to investigate theoretical predictions regarding the evolutionary pressures that drive the transition from isogamy to anisogamy, particularly in relation to gamete size differentiation and sexual selection. Its minimal gamete dimorphism and facultative parthenogenesis enable a rare window into early evolutionary steps toward anisogamy.

RESULTS: By analyzing the expression profiles of sex-biased genes (SBGs) during gametogenesis, we found that SBGs evolve faster than unbiased genes, driven by higher rates of non-synonymous substitution (dN), indicating that SBGs are under stronger selective pressures. Mating type minus-biased genes (mt-BGs) exhibit higher dN/dS values than mating type plus-biased genes (mt+BGs), suggesting stronger selective pressures on mt-BGs, although this difference was not statistically significant (P = 0.08). Using branch-site and RELAX models, we found positive selection and relaxed purifying selection acting on a significant proportion of SBGs, particularly those associated with flagella function.

CONCLUSIONS: This study highlights the selective pressures shaping anisogamy and provides insights into the molecular mechanisms underlying its evolution. The faster evolution of SBGs, particularly mt-BGs, and the positive selection on genes associated with motility, such as those related to flagella function, suggest the importance of enhanced gamete motility in the transition to anisogamy. These findings contribute to our understanding of sexual selection and the evolutionary forces that drive the differentiation of gamete size and number between sexes.

PMID:40346481 | DOI:10.1186/s12862-025-02382-y

Categories: Literature Watch

Evaluating large language model workflows in clinical decision support for triage and referral and diagnosis

Fri, 2025-05-09 06:00

NPJ Digit Med. 2025 May 9;8(1):263. doi: 10.1038/s41746-025-01684-1.

ABSTRACT

Accurate medical decision-making is critical for both patients and clinicians. Patients often struggle to interpret their symptoms, determine their severity, and select the right specialist. Simultaneously, clinicians face challenges in integrating complex patient data to make timely, accurate diagnoses. Recent advances in large language models (LLMs) offer the potential to bridge this gap by supporting decision-making for both patients and healthcare providers. In this study, we benchmark multiple LLM versions and an LLM-based workflow incorporating retrieval-augmented generation (RAG) on a curated dataset of 2000 medical cases derived from the Medical Information Mart for Intensive Care database. Our findings show that these LLMs are capable of providing personalized insights into likely diagnoses, suggesting appropriate specialists, and assessing urgent care needs. These models may also support clinicians in refining diagnoses and decision-making, offering a promising approach to improving patient outcomes and streamlining healthcare delivery.

PMID:40346344 | DOI:10.1038/s41746-025-01684-1

Categories: Literature Watch

Rapid mimicry of trunk and head movements during play in African Savanna elephants (Loxodonta africana)

Fri, 2025-05-09 06:00

Sci Rep. 2025 May 9;15(1):16263. doi: 10.1038/s41598-025-01067-2.

ABSTRACT

The basic forms of motor and possibly emotion replication include behavioral contagion and rapid motor mimicry (RMM). RMM-mainly demonstrated during play-occurs when an individual perceives and rapidly (< 1 s) replicates the exact motor sequence of another individual. We collected data on an African Savanna Elephant (Loxodonta africana; N = 15) group housed at the Parque de la Naturaleza de Cabárceno (Spain) on play target movements of both trunk and head. We demonstrated the presence of RMM. Elephants that were more prone in mimicking others' target movements were also more prone to play after observing others playing. RMM-as behavioral contagion-can enhance action coordination between players. As RMM was associated with more offensive play patterns than unreplicated target movements, RMM may allow competitive play sessions to occur, possibly replacing agonistic interactions. Neither individual (age, sex) nor social (affiliation levels) factors modulated the RMM. These findings can be related to the elephant high tolerance levels and the wide presence of play across age (including adults) and sex. Concluding, African elephants have the potential to share their affective states (emotional contagion) via RMM which is relevant to the investigation of the evolution of empathy in mammals including humans.

PMID:40346099 | DOI:10.1038/s41598-025-01067-2

Categories: Literature Watch

Self-propagating wave drives morphogenesis of skull bones in vivo

Fri, 2025-05-09 06:00

Nat Commun. 2025 May 9;16(1):4330. doi: 10.1038/s41467-025-59164-9.

ABSTRACT

Cellular motion is a key feature of tissue morphogenesis and is often driven by migration. However, migration need not explain cell motion in contexts where there is little free space or no obvious substrate, such as those found during organogenesis of mesenchymal organs including the embryonic skull. Through ex vivo imaging, biophysical modeling, and perturbation experiments, we find that mechanical feedback between cell fate and stiffness drives bone expansion and controls bone size in vivo. This mechanical feedback system is sufficient to propagate a wave of differentiation that establishes a collagen gradient which we find sufficient to describe patterns of osteoblast motion. Our work provides a mechanism for coordinated motion that may not rely upon cell migration but on emergent properties of the mesenchymal collective. Identification of such alternative mechanisms of mechanochemical coupling between differentiation and morphogenesis will help in understanding how directed cellular motility arises in complex environments with inhomogeneous material properties.

PMID:40346043 | DOI:10.1038/s41467-025-59164-9

Categories: Literature Watch

Computationally designed proteins mimic antibody immune evasion in viral evolution

Fri, 2025-05-09 06:00

Immunity. 2025 May 6:S1074-7613(25)00178-5. doi: 10.1016/j.immuni.2025.04.015. Online ahead of print.

ABSTRACT

Recurrent waves of viral infection necessitate vaccines and therapeutics that remain effective against emerging viruses. Our ability to evaluate interventions is currently limited to assessments against past or circulating variants, which likely differ in their immune escape potential compared with future variants. To address this, we developed EVE-Vax, a computational method for designing antigens that foreshadow immune escape observed in future viral variants. We designed 83 SARS-CoV-2 spike proteins that transduced ACE2-positive cells and displayed neutralization resistance comparable to variants that emerged up to 12 months later in the COVID-19 pandemic. Designed spikes foretold antibody escape from B.1-BA.4/5 bivalent booster sera seen in later variants. The designed constructs also highlighted the increased neutralization breadth elicited by nanoparticle-based, compared with mRNA-based, boosters in non-human primates. Our approach offers targeted panels of synthetic proteins that map the immune landscape for early vaccine and therapeutic evaluation against future viral strains.

PMID:40345199 | DOI:10.1016/j.immuni.2025.04.015

Categories: Literature Watch

Comparative analysis of gene regulation in single cells using Compass

Fri, 2025-05-09 06:00

Cell Rep Methods. 2025 Apr 30:101035. doi: 10.1016/j.crmeth.2025.101035. Online ahead of print.

ABSTRACT

Single-cell multi-omics is a transformative technology that measures both gene expression and chromatin accessibility in individual cells. However, most studies concentrate on a single tissue and are unable to determine whether a gene is regulated by a cis-regulatory element (CRE) in just one tissue or across multiple tissues. We developed Compass for comparative analysis of gene regulation across a large number of human and mouse tissues. Compass consists of a database, CompassDB, and an open-source R software package, CompassR. CompassDB contains processed single-cell multi-omics data of more than 2.8 million cells from hundreds of cell types. Building upon CompassDB, CompassR enables visualization and comparison of gene regulation across multiple tissues. We demonstrated that CompassR can identify CRE-gene linkages specific to a tissue type and their associated transcription factors in real examples.

PMID:40345198 | DOI:10.1016/j.crmeth.2025.101035

Categories: Literature Watch

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