bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular mechanisms of early brain overgrowth in autistic children: elevated levels of GPX4 and resistance to ferroptosis
Authors: Chen Siwei , Shcherbina Anna , Schafer Simon T. , Mattingly Zoe Alexandra , Ramesh Janani , Narayanan Cyndhavi , Banerjee Sravani , Heath Brianna , Regester Melissa , Chen Ivette , Thakurela Sudhir , Hallmayer Joachim , O’Hara Ruth , Solomon Marjorie , Nordahl Christine Wu , Amaral David G. , Chetty Sundari
Published: February 2025

Autistic individuals with disproportionate megalencephaly (ASD-DM), characterized by enlarged brains relative to body height, have higher rates of intellectual disability and face more severe cognitive challenges than autistic children with average brain sizes. The cellular and molecular mechanisms underlying this neurophenotype remain poorly understood. To investigate these mechanisms, we generated human induced pluripotent stem cells from non-autistic typically developing children and autistic children with and without disproportionate megalencephaly. We assessed these children longitudinally from ages two to twelve years using magnetic resonance imaging and comprehensive cognitive and medical evaluations. We show that neural progenitor cells (NPCs) derived from ASD-DM children exhibit increased rates of cell survival and suppressed cell death, accompanied by heightened oxidative stress and ferrous iron accumulation. Despite these stressors, ASD-DM NPCs actively suppress apoptosis and ferroptosis by regulating proteins such as caspase-3 (CASP3), poly(ADP-ribose) polymerase 1 (PARP1), and glutathione peroxidase 4 (GPX4). Cellular ferroptotic signatures are further supported by elevated expression of selenocysteine genes, includingGPX4, in the blood of ASD-DM children and their mothers, suggesting potential hereditary or environmental influences. Furthermore, we show that peripheral expression ofGPX4and other selenocysteine genes correlate with cognitive outcomes (IQ). These findings underscore the role of ferroptosis in autism, pointing to potential diagnostic biomarkers and targets for intervention.
Pathological mutation in SMN impairs modulation of GAR1 phase separation linking condensate dysfunction to Spinal Muscular Atrophy
Authors: Félix Sara S. , O’Toole Philip , Oliveira Nuno A. S. , Pinho Brígida R. , Blacker Thomas S. , Fernandes Fábio , Oliveira Jorge M. A. , Oroz Javier , Laurents Douglas V. , Cabrita Eurico J.
Published: February 2025

Pathological mutations in liquid-liquid phase separation (LLPS) scaffold proteins have been linked to biomolecular condensate dysfunction in neurodegenerative diseases, while the possible impact of client protein mutations remains unclear. In spinal muscular atrophy (SMA), the disease-associated E134K mutation in the Tudor domain (TD) of the survival motor neuron (SMN) protein disrupts its interaction with GAR1, an RGG-rich protein within the H/ACA small nucleolar ribonucleoprotein complex. The consequences of this impaired interaction have not been elucidated. Here, we identified GAR1 as an LLPS scaffold protein that is phase separated in nuclear compartments and forms gel-like condensates via complex coacervation with RNAin vitro. In cells, we reveal that SMN co-localizes with GAR1 in Cajal bodies and modulates its dynamics. Using confocal microscopy and NMR spectroscopy, we further show that SMN TD is a client protein that regulates the architecture and dynamics of GAR1 condensates through competitive RNA interactions, implicating GAR1 phase separation in RNA accumulation and release processes regulated by SMN. Notably, the SMA-associated E134K variant of SMN exhibits a reduced affinity for GAR1, impairing the modulation of GAR1 condensates and displacement RNA. Our findings suggest a mechanistic link between phase separation dysregulation and SMA, driven by disrupted scaffold-client interactions, that highlights the therapeutic potential of targeting SMN-dependent condensate regulation in SMA.
Parallel hierarchical encoding of linguistic representations in the human auditory cortex and recurrent automatic speech recognition systems
Authors: Keshishian Menoua , Mischler Gavin , Thomas Samuel , Kingsbury Brian , Bickel Stephan , Mehta Ashesh D. , Mesgarani Nima
Published: February 2025

The human brain’s ability to transform acoustic speech signals into rich linguistic representations has inspired advancements in automatic speech recognition (ASR) systems. While ASR systems now achieve human-level performance under controlled conditions, prior research on their parallels with the brain has been limited by the use of biologically implausible models, narrow feature sets, and comparisons that primarily emphasize predictability of brain activity without fully exploring shared underlying representations. Additionally, studies comparing the brain to text-based language models overlook the acoustic stages of speech processing, an essential part in transforming sound to meaning. Leveraging high-resolution intracranial recordings and a recurrent ASR model, this study bridges these gaps by uncovering a striking correspondence in the hierarchical encoding of linguistic features, from low-level acoustic signals to high-level semantic processing. Specifically, we demonstrate that neural activity in distinct regions of the auditory cortex aligns with representations in corresponding layers of the ASR model and, crucially, that both systems encode similar features at each stage of processing—from acoustic to phonetic, lexical, and semantic information. These findings suggest that both systems, despite their distinct architectures, converge on similar strategies for language processing, providing insight in the optimal computational principles underlying linguistic representation and the shared constraints shaping human and artificial speech processing.
Action features dominate cortical representation during natural vision
Authors: Jung Heejung , Han Xiaochun , Ma Feilong , Han Jane , Shokeen Deepanshi , Uden Cara Van , Hanson Isabella , Connolly Andrew C , Haxby James V , Nastase Samuel A
Published: February 2025

Cortical resources are allocated into systems specialized for processing ecologically relevant features of the world. These features are typically studied in isolation using controlled experimental stimuli, making it difficult to assess the relative importance of different kinds of features that tend to overlap during natural vision. In the current study, we evaluated the relative contributions of action, agent, and scene features in predicting cortical activity while participants viewed a 1-hour nature documentary. We tested four sets of model features: semantic vectors capturing the observed action, agent, and scene features derived from an annotation of the stimulus, as well as low-level visual motion-energy features. We used banded ridge regression to fit vertex-wise encoding models from the combination of all four sets of features. While each set of features predicted neural activity in the expected areas, the action features predicted more widespread activity. A variance partitioning analysis revealed that the action features captured the most unique variance in neural activity across ten times as many cortical vertices as the agent or scene features. Our findings suggest that cortical activity during dynamic, natural vision is dominated by features for understanding the actions of others.
An HIV-1 Reference Epitranscriptome
Authors: Bosmeny Michael S. , Pater Adrian A. , Zhang Li , Sha Beverly E. , Lyu Zidi , Larkai Lydia , Damha Masad J. , Mamede Joao I. , Gagnon Keith T.
Published: February 2025

Post-transcriptional chemical modifications to RNA, or the epitranscriptome, play important roles in RNA metabolism, gene regulation, and human disease, including viral pathogenesis. Modifications to the RNA viral genome and transcripts of human immunodeficiency virus 1 (HIV-1) have been reported, including methylation of adenosine (m6A) and cytosine (m5C), acetylation of cytosine, pseudouridylation (psi), and conversion of adenosine to inosine, and their effects on virus and host biology have been investigated. However, diverse experimental approaches have been used, making clear correlations across studies difficult to assess. To address this need, we propose the establishment of a reference HIV-1 epitranscriptome. We sequenced the model NL4-3 HIV-1 genome from infected Jurkat CD4+ T cells cells using the latest nanopore chemistry, custom RNA preparation methods, and commercial base-calling algorithms. This resulted in a reproducible sense and preliminary antisense HIV-1 epitranscriptome where m6A, m5C, psi, ands inosine could be identified by multiplexed base-calling. Multiplexed base-calling miscalled modifications due to sequence and neighboring modification contexts, which we demonstrate can be corrected with synthetic HIV-1 RNA fragments. We validate m6A modification sites with a small molecule inhibitor of methyltransferase-like 3 (METTL3), STM2457. We conclude that modifications do not change substantially under combination antiretroviral therapy (cART) treatment or in primary CD4+ T cells. Samples from patients living with HIV reveal conservation of certain modifications, such as m6A. Our approach and reference data offer a straightforward benchmark that can be adopted to help advance rigor, reproducibility, and uniformity across future HIV-1 epitranscriptomics studies.
Ku suppresses RNA-mediated innate immune responses in human cells to accommodate primate-specific Alu expansion
Authors: Zhu Yimeng , Li Angelina , Maji Suvrajit , Lee Brian J. , Korn Sophie M. , Gertie Jake A. , Dorrity Tyler J. , Wang Jianhua , Wang Kyle J. , Pelletier Amandine , Moakley Daniel F. , Kelly Rachel D. , Holmes Antony B. , Rabadan Raul , Edgell David R. , Schild Poulter Caroline , Modesti Mauro , Steckelberg Anna-Lena , Hendrickson Eric A. , Chung Hachung , Zhang Chaolin , Zha Shan
Published: February 2025

Ku70 and Ku80 form Ku, a ring-shaped protein that initiates the non-homologous end-joining (NHEJ) DNA repair pathway.1Specifically, Ku binds to double-stranded DNA (dsDNA) ends and recruits other NHEJ factors (e.g., DNA-PKcs and LIG4). While Ku binds to double-stranded RNA (dsRNA)2and traps mutated-DNA-PKcs on ribosomal RNAin vivo,3,4the physiological significance of Ku-dsRNA interactions in otherwise wild-type cells remains elusive. Intriguingly, while dispensable for murine development,5,6Ku is essential in human cells.7Despite similar genome sizes, human cells express ∼100-fold more Ku than mouse cells, implying functions beyond NHEJ, possibly through a dose-sensitive interaction with dsRNA, which is ∼100 times weaker than with dsDNA.2,8While investigating the essentiality of Ku in human cells, we found that depletion of Ku - unlike LIG4 - induces profound interferon (IFN) and NF-kB responses reliant on the dsRNA-sensor MDA5/RIG-I and adaptor MAVS. Prolonged Ku-degradation also activates other dsRNA-sensors, e.g. PKR that suppresses protein translation, and OAS/RNaseL that cleaves rRNAs and eventually induces growth arrest and cell death. MAVS, RIG-I, or MDA5 knockouts suppressed IFN signaling and, together with PKR knockouts, partially rescued Ku-depleted human cells. Ku-irCLIP analyses revealed that Ku binds to diverse dsRNA, predominantly stem-loops in primate-specific Alu elements9at anti-sense orientation in introns and 3’-UTRs. Ku expression rose sharply in higher primates tightly correlating with Alu-expansion (r = 0.94/0.95). Together, our study identified a vital role of Ku in accommodating Alu-expansion in primates by mitigating a dsRNA-induced innate immune response, explaining the rise of Ku levels and its essentiality in human cells.
Being bigger is better: Size-dependent advantages of plasmodial fusion in a multinucleated slime mould
Authors: Broersma Cathleen M. E. , Rozen Daniel
Published: February 2025

Larger body size often enhances survival and reproduction. While most organisms grow to achieve larger sizes, some can rapidly increase size through fusion. Fusion decisions are influenced by genetic relatedness and environmental factors, balancing potential benefits and costs. InPhysarum polycephalum, a multinucleated slime mould, fusion is thought to occur mainly between genetically identical or highly related individuals. However, the frequency of fusion among close relatives, and the drivers and benefits of fusion, remain unclear. This study explored fusion frequency, morphology, and benefits among clonal and closely related individuals ofPhysarum. We also assessed the impact of abiotic stress on fusion and whether genetic relatedness between fusion partners influences survival during exposure to stress. Our results revealed variation in fusion frequency and morphology among different plasmodial lines and pairs of close relatives. Abiotic stress increased fusion rates between both clonal and compatible non-clonal pairs. However, the benefits of fusion did not depend on the whether fusion occurred between clones or non-clones. These findings demonstrate plasmodial fusion provides size-related survival benefits. Furthermore, the promotion of fusion in stressful conditions highlights its adaptive role in responding to environmental challenges. Collectively, these results underscore the evolutionary importance of fusion inPhysarum, shaping its ecological success and resilience.

Competing Interests Statement

The authors declare no competing financial interests.
Transcriptional network analysis of PTEN protein-deficient prostate tumors reveals robust stromal reprogramming and signs of senescent paracrine communication
Authors: Rondon-Lorefice Ivana , Lopez Jose I. , Ugalde-Olano Aitziber , Zufiaurre Maite , Astobiza Ianire , Garcia-Longarte Saioa , Zabala Amaia , Rey Sofia , Santos-Martin Aida , Unda Miguel , Loizaga-Iriarte Ana , Graupera Mariona , Nuciforo Paolo , Carracedo Arkaitz , Mendizabal Isabel
Published: February 2025

Among the extensive genomic alterations in prostate cancer, the genomic deletion ofPTENstands out as one of the most consistently observed and confirmed alteration.PTENloss in prostate tumors is primarily associated with cancer cell proliferation and survival through the activation of the PI3K-AKT-mTOR signalling pathway. However, its use as a robust biomarker in the clinical practice is hampered by the complex epigenetic, transcriptional and post-translational regulation. Here, we undertook an approach that combinedin situassessment of PTEN protein with transcriptional surrogates of its activity to gain insights into the downstream functional effects of PTEN loss in primary tumors. Our extensive bioinformatic analyses, including the integration with single-cell RNA-Seq approaches in a new clinical cohort, highlighted stroma remodeling as the major cancer cell-extrinsic process associated with PTEN loss. By applying similar computational strategy on the transcriptomic data generated from primary prostate tumors of genetically engineeredPten knock-outmouse models, we validated the causal role ofPtenin the stromal reaction observed in clinical specimens. Mechanistically, we provide evidence for the activation of a paracrine program that encompasses enhanced TGF-β signalling and that is compatible with the secretome of PTEN-deficient senescent cancer cells. Our study provides relevant biological context to the cellular and molecular alterations unleashed upon PTEN protein loss.
The core MICOS complex subunit Mic60 has been substituted by two cryptic mitofilin-containing proteins in Euglenozoa
Authors: Sheikh Shaghayegh , Turpin Knotková Barbora , Benz Corinna , Eliáš Marek , Bílý Tomáš , Bondar Alexey , Tesařová Martina , Stríbrná Eva , Heller Jiří , Meinecke Michael , Hashimi Hassan
Published: February 2025

Cristae enclose respiratory chain protein complexes, making them the bioenergetic subcompartments of mitochondria. The MICOS complex is among the inducers of sharp membrane curvature needed for crista formation. Resembling the respiratory chain complexes, MICOS is organized around a core protein, the mitofilin-domain bearing Mic60, that was inherited from the alphaproteobacterial progenitor of mitochondria. Extant alphaproteobacteria express Mic60 to form their own bioenergetic subcompartments, demonstrating the permeance of Mic60’s form and function during the long span of prokaryotic and eukaryotic evolution. Yet, unlike virtually all aerobic eukaryotes, Mic60 is not encoded in any genome of the multifarious protists that comprise the phylum Euglenozoa, including trypanosomes. Here, we show that Mic60 has been replaced in euglenozoans by two cryptic mitofilin domain-containing MICOS subunits, Mic34 and Mic40. Sharply contrasting Mic60 from two domains of life, these are not integral membrane proteins. Reverse genetics revealed they are intertwined with the oxidative protein folding pathway required for mitochondrial–and crista–biogenesis, veiling a potential membrane remodeling role. Nevertheless, Mic34 binds to phospholipid bilayersin vitro. Mic34 and Mic40 heterologous expression remodels gammaproteobacterial cytoplasmic membranes, like prokaryotic and eukaryotic Mic60. Astoundingly, Mic34 overexpression elaborates the simplified tubular mitochondrion of aTrypanosoma bruceilife cycle stage with repressed oxidative phosphorylation. The structural correspondence of Mic34’s mitofilin domain to Mic60’s predicted mutations to conserved motifs that ablated Mic34’s mitochondria-remodeling activity. Thus, the mitofilin protein family is more diverse than originally supposed, with two of its structurally most divergent members altering the core of euglenozoan MICOS.

SIGNIFICANCE STATEMENT

Cristae are mitochondrial subcompartments that give the organelle its distinctive ruffled appearance. They house multiprotein-complex machinery needed for cellular respiration. These crista-embedded complexes are built around an immutable protein core inherited from the bacterial symbiont that engendered mitochondria. Mic60 represents one such core protein. Because of its fundamental role in crista formation, Mic60 is present in virtually all organisms with cristae, and even in the closest known bacterial relatives of mitochondria, reflecting Mic60’s symbiotic origin. Euglenozoan protists are a strange exception, lacking a recognizable Mic60 despite having cristae. Instead, they have two cryptic Mic60-like proteins that evaded recognition due to their radically altered structures. This demonstrates that even the normally conserved cores of ancient protein complexes can change during evolution.
High throughput protein serial crystallography using a grease matrix and a large-area support film
Authors: Sugahara Michihiro , Maki-Yonekura Saori , Inoue Ichiro , Takaba Kiyofumi , Narai Shun , Naitow Hisashi , Kang Jungmin , Tono Kensuke , Numata Keiji , Ishikawa Tetsuya , Yabashi Makina , Yonekura Koji
Published: February 2025

Serial femtosecond crystallography (SFX) using ultrashort pulses from X-ray free- electron lasers (XFELs) enables the determination of crystal structures at room temperature while minimizing radiation damage to the samples. This method involves irradiating numerous crystals one by one with XFEL pulses, allowing even the capture snapshots of dynamical structures in biological macromolecules. To achieve this, an efficient sample delivery system is essential for acquiring a large number of diffraction patterns. The most common approach uses a highly viscous grease matrix containing sample crystals, injected into the XFEL path from a narrow nozzle. However, the injection often suffers from clogging issues inside the injector nozzle, resulting in additional challenges such as the need for suitably sized crystals, increased sample consumption and unstable flow rates. Alternatively, a fixed-target approach, which scans a two-dimensional substrate with dispersed samples, can circumvent these issues. However, it must ensure the integrity of biological samples and provide sufficient surface area for efficient data collection. We here present an approach that utilizes a grease matrix and a large-area support film specially designed to address these requirements. This system offers a fast and reliable solution for protein SFX, enabling high-quality structure determination while significantly reducing sample consumption.
Structural and Functional Versatility of the Amyloidogenic Antimicrobial Peptide Citropin 1.3
Authors: Strati Fabio , Cali Mariana Pigozzi , Bloch Yehudi , Mostafavi Siavash , Monistrol Jim , Golubev Aleksandr , Rayan Bader , Gustavsson Emil , Landau Meytal
Published: February 2025

Citropin 1.3 is an antimicrobial peptide produced by the amphibianLitoria citropa(Southern bell frog), which self-aggregates into distinct fibrillar structures, however, the function of the fibrils remains unclear and largely unexplored. In this study, the structural and functional properties of citropin 1.3 were investigated using cryogenic electron microscopy and fluorescence microscopy in the presence of membrane and cell models, and with X-ray crystallography. Canonical amyloids, multilayered nanotubes, and a novel mixed fibril were observed. Experiments with negatively charged giant unilamellar vesicles revealed that the peptide facilitates membrane fusion while simultaneously undergoing phase separation in the presence of phospholipids. In presence of mammalian cells, citropin 1.3 permeabilizes membranes, leading to cell death, and over time, colocalizes with genetic material. Overall, this work provides new insights into the structural dynamics of the amyloidogenic antimicrobial peptide citropin 1.3 and its interactions with different systems.
Phylodynamic estimation of the within-host mutation rate of extended-spectrum beta-lactamase-producing Enterobacterales
Authors: Windels Etthel M. , Aguilar-Bultet Lisandra , Vock Isabelle , Maurer Perkerman Laura , Tschudin-Sutter Sarah , Stadler Tanja
Published: February 2025

Despite their clinical relevance, the within-host evolution of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) is still poorly understood. To estimate the within-host mutation rates of ESBL-producingEscherichia coliandKlebsiella pneumoniaespecies complex, we fitted phylodynamic models to genomic sequence data of longitudinally collected rectal swabs from 64 colonized hospital patients. We estimated an average within-host mutation rate of 7.71e-07 [4.60e-07,1.10e-06] mutations/site/year forE. coliand 4.20e-07 [1.57e-07,7.14e-07] mutations/site/year forK. pneumoniaespecies complex, with limited variation observed across patients and sequence types. These estimates are presumably the most accurate reported so far and are useful for future epidemiological and evolutionary studies.

Impact statement

Understanding the within-patient mutation rates of extended-spectrum beta-lactamase (ESBL)-producingE. coliandK. pneumoniaespecies complex is critical for elucidating their evolutionary dynamics and transmission potential. In this study, we employed Bayesian phylodynamic models to analyze longitudinal isolates collected over a 10-year period from hospitalized patients. Our findings reveal limited variability in mutation rates across patients and sequence types, suggesting evolutionary stability within these pathogens in hospital settings. This work provides new insights into the persistence and evolutionary dynamics of ESBL-PE, offering valuable guidance for antimicrobial resistance surveillance and infection prevention strategies.

Data summary

The data used in this study are publicly available in the NCBI database under the BioProject number PRJNA910977. Supporting metadata are provided in Appendix 1. The code for the phylodynamic analyses, including the BEAST2 XML files, is available athttps://github.com/EtthelWindels/esbl-pe_mutation. All supporting data, code and protocols have been provided within the article, supplementary data files or public repositories.
SEVI Fibrils are Induced by Bacterial Surface Molecules and Exert Antimicrobial Activity Against ESKAPE Pathogens
Authors: Vogel Verena , Olari Lia-Raluca , Bauer Richard , Burczyk Sandra , Witz Fiona , Walker Emely , Jaber Nourice , Rupp Ulrich , Stifel Ulrich , Zinngrebe Julia , Read Clarissa , Fischer-Posovszky Pamela , Münch Jan , Spellerberg Barbara
Published: February 2025

The semen-derived enhancer of viral infection (SEVI) is an amyloid fibril formed by the self-assembly of the PAP248-286 peptide, a cleavage product of prostatic acid phosphatase, which is naturally present in human seminal plasma. SEVI is known to enhance HIV-1 infection by promoting virion attachment to cells, potentially facilitating sexual spread. Beyond its role in HIV transmission, findings highlight a physiological function for SEVI in innate immunity. As many amyloids display antimicrobial effects, we tested SEVI fibrils for antibacterial activity against microbial ESKAPE pathogens and urogenital bacteria, includingPseudomonas aeruginosa, Klebsiella quasipneumoniae, Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, Streptococcus agalactiaeandListeria monocytogenes. SEVI exhibited direct dose-dependent antibacterial effects in radial diffusion and survival assays, with activity observed at physiologically relevant concentrations. Bacterial surface molecules such as lipopolysaccharides and lipoteichoic acid induced the formation of SEVI fibrils, as confirmed by kinetic assays. Preincubation with epigallocatechin gallate, a fibril disruptor, abolished SEVI’s antibacterial activity, pointing to the importance of its fibrillar structure. Mechanistic studies and electron microscopy revealed limited bacterial membrane disruption and the intracellular accumulation of polyphosphate granules inP. aeruginosa, indicating a stress response. In conclusion, SEVI exerts a potent antibacterial activity against pathogens found in the urogenital tract indicating a potential physiological role in vaginal mucosal immunity.
Tsc1Deletion in Purkinje Neurons Disrupts the Axon Initial Segment, Impairing Excitability and Cerebellar Function
Authors: Brown Samuel P. , Jena Achintya K. , Osko Joanna J. , Ransdell Joseph L.
Published: February 2025

Loss-of-function mutations in tuberous sclerosis 1 (TSC1) are prevalent monogenic causes of autism spectrum disorder (ASD). Selective deletion ofTsc1from mouse cerebellar Purkinje neurons has been shown to cause several ASD-linked behavioral impairments, which are linked to reduced Purkinje neuron repetitive firing rates. We used electrophysiology methods to investigate why Purkinje neuron-specificTsc1deletion (Tsc1mut/mut) impairs Purkinje neuron firing. These studies revealed a depolarized shift in action potential threshold voltage, an effect that we link to reduced expression of the fast-transient voltage-gated sodium (Nav) current inTsc1mut/mutPurkinje neurons. The reduced Nav currents in these cells was associated with diminished secondary immunofluorescence from anti-pan Nav channel labeling at Purkinje neuron axon initial segments (AIS). Interestingly, anti-ankyrinG immunofluorescence was also found to be significantly reduced at the AIS ofTsc1mut/mutPurkinje neurons, suggesting Tsc1 is necessary for the organization and functioning of the Purkinje neuron AIS. An analysis of the 1stand 2ndderivative of the action potential voltage-waveform supported this hypothesis, revealing spike initiation and propagation from the AIS ofTsc1mut/mutPurkinje neurons is impaired compared to age-matched control Purkinje neurons. HeterozygousTsc1deletion resulted in no significant changes in the firing properties of adult Purkinje neurons, and slight reductions in anti-pan Nav and anti-ankyrinG labeling at the Purkinje neuron AIS, revealing deficits in Purkinje neuron firing due toTsc1haploinsufficiency are delayed compared to age-matchedTsc1mut/mutPurkinje neurons. Together, these data reveal the loss ofTsc1impairs Purkinje neuron firing and membrane excitability through the dysregulation of proteins necessary for AIS organization and function.
Evening blue light exposure during adolescence induces avoidance behaviors and rewires medial amygdala circuit
Authors: Bonilla Pablo , McBride David , Shanks Alexandria , Kartik Janhvi , Bhan Ashita , Porcu Alessandra
Published: February 2025

Adolescents are being increasingly exposed to artificial blue light from electronic devices, raising concerns about its effects on brain development and mental health. The medial amygdala (MeA), a brain region critical for emotional regulation, is light-sensitive, yet how evening blue light during puberty influences its circuitry and behavior remains unknown.

Using a light cycle disruption paradigm, we found that adolescent mice exposed to evening blue light displayed increased avoidance behaviors compared to those exposed to darkness or reduced blue light conditions. Single-nuclei RNA sequencing revealed altered cell-type composition and disrupted synaptic communication pathways in the MeA.In vivocalcium imaging showed increased activity in MeA somatostatin neurons during avoidance behaviors, while chemogenetic inhibition of these neurons reduced these behaviors.

Our findings identify the MeA as a key integrator of emotional responses to environmental blue light, suggesting evening blue light exposure during puberty as a potential risk factor for affective disorders.

Teaser

Evening blue light exposure during adolescence alters medial amygdala functions, leading to anxiety-like behaviors.
Dependence of cell fate potential and cadherin switching on primitive streak coordinate during differentiation of human pluripotent stem cells
Authors: Zhu Ye , Warmflash Aryeh
Published: February 2025

During gastrulation, the primitive streak (PS) forms and begins to differentiate into mesendodermal subtypes. This process involves an epithelial-mesenchymal transition (EMT), which is marked by cadherin switching, where E-Cadherin is downregulated, and N-Cadherin is upregulated. To understand the relationships between differentiation, EMT, and cadherin switching, we made measurements of these processes during differentiation of human pluripotent stem cells (hPSCs) to PS and subsequently to mesendoderm subtypes using established protocols, as well as variants in which signaling through key pathways including Activin, BMP, and Wnt were modulated. We found that perturbing signaling so that cells acquired identities ranging from anterior to posterior PS had little impact on the subsequent differentiation potential of cells but strongly impacted the degree of cadherin switching. The degree of E-Cadherin downregulation and N-Cadherin upregulation were uncorrelated and had different dependence on signaling. The exception to the broad potential of cells throughout the PS was the loss of definitive endoderm potential in cells with mid to posterior PS identities. Thus, cells induced to different PS coordinates had similar potential within the mesoderm but differed in cadherin switching. Consistently, E-Cadherin knockout did not alter cell fates outcomes during differentiation. Overall, cadherin switching and EMT are modulated independently of cell fate commitment in mesendodermal differentiation.
A brainstem-thalamic circuitry for affective-motivational responses to cold pain
Authors: Reddy Prannay , Okuda Takao , Rani Mousmi , Prajapati Jagat Narayan , Koul Smriti , Samineni Vijay , Barik Arnab
Published: February 2025

The medial thalamus is crucial for the sensory and affective-motivational responses to chronic pain. However, a mechanistic understanding of how the distinct subnuclei of the medial thalamus mediate behavioral responses to pain remains lacking. Taking advantage of intersectional viral genetics, chemogenetics, optogenetics, in-vivo imaging, and ex-vivo physiology, we reveal that the neurons in the parafascicular (PF) nuclei of the medial thalamus receive monosynaptic inputs from the lateral parabrachial nuclei (LPBN) in mice. LPBN is an essential nucleus in the ascending pain pathway, receiving projections from the dorsal horn of the spinal cord. The PF neurons downstream of LPBN (PFpost-LPBN) are nociceptive, sensitized by peripheral neuropathy, acutely aversive, and, when activated, drive both sensory and affective-motivational responses to cold pain. In contrast, the LPBN target neurons in the intralaminar centromedian thalamus (CMpost-LPBN), another nociceptive nucleus of the medial thalamus, are primarily involved in the affective-motivational aspects of pain. Together, we reveal that the LPBN, through two closely related thalamic nuclei, influences behavior in mice with cold hypersensitivity due to peripheral neuropathies.
Efferent signaling along nociceptive peripheral terminalsin vivois enhanced during inflammation
Authors: Gershon Devora , Barkai Omer , Engelmayer Nurit , Katz Ben , Lev Shaya , Binshtok Alexander M
Published: February 2025

Primary nociceptors are essentially characterized as afferent neurons carrying noxious sensory information from the periphery to the CNS. However, the information flow on primary nociceptors is bidirectional. Nociceptor peripheral terminals release a variety of mediators to the target organ in the vicinity of the injured area. These mediators promote sensitization of adjacent sensory neurons, vasodilation, and edema and affect innate and adaptive immunity, leading to hyperalgesia and inflammation that often expands beyond the injured areas. Many theories associate these phenomena with the antidromic action potential propagation along nociceptor terminals; however, the antidromic efferent signaling at the single nociceptor terminals has never been demonstrated. Here, usingin vivocalcium imaging from the individual nociceptive terminals innervating the mouse cornea together with a computational approach, we demonstrated that short-lasting activation of a single terminalin vivowas sufficient to activate the remote, non-activated terminal, which branches from the same nociceptor fiber. This increase was dependent on the activation of voltage-gated sodium and calcium channels. Moreover, we showed that the efferent signaling along nociceptive terminals increases under inflammatory conditions, culminating in enhanced calcium signaling in the remote non-activated terminals. This inflammation-induced increase in intra-terminal calcium could trigger the enhanced release of inflammatory mediators, spilling over wider areas and affecting terminals from adjacent unstimulated receptive fields, leading to the expansion of hyperalgesia and inflammation.
The impact of education quality indicators on students’ satisfaction
Authors: Ikram Maryam , Saleem Syed Muhammad Umer , Mehmood Waqas
Published: February 2025

Purpose

This study aims to determine the impact of the United Nations Educational, Scientific and Cultural Organisation (UNESCO) education quality indicators nexus using teaching and learning materials, physical infrastructure and facilities, teaching methods and assessment on students’ satisfaction (SS) in Pakistani higher education institutions (HEIs).

Design/methodology/approach

An investigation was conducted using empirical research involving 440 postgraduate students from 11 private universities in Lahore, Punjab Province, Pakistan. Data were collected through an online questionnaire. Participants were selected using a stratified sampling technique, and the data were analysed using partial least squares structural equation modelling.

Findings

The findings proved the existence of a significant and positive relationship between teaching and learning materials, physical infrastructure and facilities, teaching methods and assessment of SS in Pakistani HEIs.

Originality/value

The novelty of this article lies in the fact that it addresses the gap in the existing literature by exploring the impact of teaching and learning materials, physical infrastructure and facilities, teaching methods, assessment and student satisfaction in the context of private higher education in Pakistan.
Going beyond the surface: the nexus between decent work, faculty engagement and intrinsic religiosity in Pakistan’s higher education institutions
Authors: Afzal Muhammad Adnan , Hussain Khalid , Aamir Muhammad , Rehan Muhammad Farooq , Khan Shoaib Masood
Published: February 2025

Purpose

This study examines the impact of five dimensions of decent work on the faculty engagement in Pakistan’s higher education institutions. Furthermore, it examines the moderating influence of intrinsic religiosity on the associations above.

Design/methodology/approach

This research employed a cross-sectional approach to collect data from 542 faculty members working with higher education institutions through electronic and in-person questionnaire administration.

Findings

The findings indicate that safe interpersonal working conditions, opportunities for free time and rest, adequate compensation, and the availability of healthcare services significantly positively impact the level of work engagement among faculty members. Additionally, the research revealed that intrinsic religiosity reinforces the previously established significant associations.

Research limitations/implications

The research acknowledges specific constraints that could impact the applicability of its findings, including the utilization of a cross-sectional methodology, the dependence on self-reported information, and the possibility of sample biases. Subsequent investigations may rectify these constraints to provide a more all-encompassing comprehension of the subject matter.

Practical implications

The findings possess practical significance for the management of HEIs in cultivating an ideal working atmosphere for faculty members. Ensuring adequate compensation, secure working environments and healthcare accessibility is underscored to enhance faculty engagement. Furthermore, acknowledging the significance of intrinsic religiosity can improve faculty engagement.

Originality/value

This research contributes to the current body of literature by investigating the complex relationship among decent work, faculty engagement, and intrinsic religiosity in the specific context of higher education institutions in Pakistan.
A case of warts in toe webs due to HPV type 7: Case report and literature review
Authors: Tochigi Mei , Takamiya Yuko , Ochiai Sawako , Anzawa Kazushi , Tsutsui Kiyohiro , Shimizu Akira
Published: February 2025

“Butcher's warts” are skin lesions caused by human papillomavirus type 7 (HPV type 7). Another clinically distinctive lesion, “warts in toe webs” (WTW), localized between the toes, has also been reported but remains poorly understood. We report the case of an 84‐year‐old man with a refractory, cauliflower‐like lesion between his toes which was unresponsive to yokuinin and liquid nitrogen cryotherapy. The patient had no history of meat of fish handling. Biopsy revealed papillary thickening of the stratum corneum and vacuolated cells. Polymerase chain reaction and immunohistochemistry analysis confirmed HPV type 7. Treatment modifications, including maintaining a dry interdigital environment, led to resolution within 2 months. Our review of 19 previously reported WTW cases indicates a distinct clinical profile: all cases involved males from Asia, with a prevalence of fungal coinfection. This case indicates the importance of HPV typing for diagnosis and maintaining a dry interdigital environment to enhance treatment outcomes.
Methods to prevent overdevelopment of fingermarks with 1,2‐indanedione/zinc
Authors: Choi Hongjin , Kwon Nokyeon , Kim Jiwon , Park Dasom , Cheon Jimin , Hong Sungwook
Published: February 2025

A piece of paper submitted as evidence can both have fingermarks with a high and low amount of sweat. When such paper is treated with 1,2‐indanedione/zinc and subsequently heated at 160°C for 10 s, fingermarks with high sweat content may become overdeveloped. Attempts to prevent overdevelopment by reducing the heating time to <10 s were ineffective. However, it was found that maintaining the heating time at 10 s and reducing the temperature to below 160°C effectively prevented overdevelopment. In forensic practice involving latent fingermarks on actual evidence, an effective enhancement technique involves initially placing approximately 15 sheets of paper between the sample and an iron preheated to 160°C, and then applying heat for 10 s. This is subsequently followed by a secondary heating without the paper. This procedure has proven effective in enhancing fingermarks with both high and low sweat contents.
Improve the visualization effect of fingerprint immunolabeling based on biotin‐avidin system
Authors: Liu Xiao‐Peng , Liang Mu‐Wen , Du Bin , Zhao Ya‐Bin , Tong Zhao‐Yang
Published: February 2025

Immunolabeling based on fluorescence is a new technique that has been recently applied in the field of forensic science. In this paper, a new immunofluorescence method based on signal amplification was applied to develop fingermarks and improve the quality of pattern recognition with clear ridge details and high contrast. The high affinity between biotin and avidin and the one‐to‐many binding mode can connect several fluorescent groups together to achieve a signal amplification effect. The results indicated that the fluorescence intensity of the fingermark sample, as displayed by the biotin‐avidin signal amplification system (BAS), was nearly three times higher than that revealed by previous immunolabeling methods based on fluorescence. Specifically, more fluorescent chromophores were bound to the friction ridges in BAS. Two proteins were selected as experimental target proteins for fingermark immunofluorescence visualization to optimize the visualization effect. The results showed that compared to keratin 1, dermcidin as the target protein in BAS achieved a more desirable effect, with 88.9% of the experimental samples left on nonporous objects having identification value. This method provides new insights for the development of fingermark spectra and is expected to become an effective and safe technology in the field of forensic science.
Effect of lotus rhizome residue on the quality and nutritional properties of wheat‐based noodles
Authors: Duan Ruibing , Huang Zhenfu , Chen Xianqiang , Liu Yanzhao , Li Jie , Yan Shoulei
Published: February 2025

Lotus rhizome residue (LRr), the primary byproduct of lotus rhizome processing, is abundant in dietary nutrients such as dietary fiber and polyphenols. To enhance the utilization efficiency of LRr and develop noodles with elevated nutritional value, this study investigates the impact of LRr on cooking and nutritional characteristics of noodles. The results showed that the addition of LRr increased the viscoelasticity of dough, but when the amount of LRr was 10%, the viscoelasticity decreased. The addition of 2%–6% LRr can effectively mitigate cooking loss and enhance noodle expansion rate. However, excessive addition results in elevated cooking loss and diminished expansion rate. The reduction in β‐sheet and disulfide bond content within gluten, along with the observed structural looseness of dough, are the primary factors contributing to the aforementioned phenomenon. The noodles prepared using the optimal formula exhibited a significant improvement in both phenol and dietary fiber content. Specifically, the dietary fiber content increased from 4% to 11.5%, and the expected glycemic index will decrease from 81.3 to 72.5. The present study establishes a fundamental basis for enhancing the economic value of byproducts from lotus rhizome industry and for innovating formulations of high‐fiber noodle.

Practical Application

When the amount of LRrt was 10%, the dietary fiber content increased from 4% to 11.5% and expected glycemic index will decrease from 81.3 to 72.5. In comparison to whole wheat noodles, LRr noodles presented significant merits in terms of antioxidant capacity and glycemic index. Not only do LRr noodles serve as a premium source of polyphenols, flavonoids, and dietary fiber but they also exhibit a notably lower eGI.
Benchmarking tree species classification from proximally sensed laser scanning data: Introducing the FOR‐species20K dataset
Authors: Puliti Stefano , Lines Emily R. , Müllerová Jana , Frey Julian , Schindler Zoe , Straker Adrian , Allen Matthew J. , Winiwarter Lukas , Rehush Nataliia , Hristova Hristina , Murray Brent , Calders Kim , Coops Nicholas , Höfle Bernhard , Irwin Liam , Junttila Samuli , Krůček Martin , Krok Grzegorz , Král Kamil , Levick Shaun R. , Luck Linda , Missarov Azim , Mokroš Martin , Owen Harry J. F. , Stereńczak Krzysztof , Pitkänen Timo P. , Puletti Nicola , Saarinen Ninni , Hopkinson Chris , Terryn Louise , Torresan Chiara , Tomelleri Enrico , Weiser Hannah , Astrup Rasmus
Published: February 2025

Proximally sensed laser scanning presents new opportunities for automated forest ecosystem data capture. However, a gap remains in deriving ecologically pertinent information, such as tree species, without additional ground data. Artificial intelligence approaches, particularly deep learning (DL), have shown promise towards automation. Progress has been limited by the lack of large, diverse, and, most importantly, openly available labelled single‐tree point cloud datasets. This has hindered both (1) the robustness of the DL models across varying data types (platforms and sensors) and (2) the ability to effectively track progress, thereby slowing the convergence towards best practice for species classification.

To address the above limitations, we compiled the FOR‐species20K benchmark dataset, consisting of individual tree point clouds captured using proximally sensed laser scanning data from terrestrial (TLS), mobile (MLS) and drone laser scanning (ULS). Compiled collaboratively, the dataset includes data collected in forests mainly across Europe, covering Mediterranean, temperate and boreal biogeographic regions. It includes scattered tree data from other continents, totaling over 20,000 trees of 33 species and covering a wide range of tree sizes and forms. Alongside the release of FOR‐species20K, we benchmarked seven leading DL models for individual tree species classification, including both point cloud (PointNet++, MinkNet, MLP‐Mixer, DGCNNs) and multi‐view 2D‐based methods (SimpleView, DetailView, YOLOv5).

2D Image‐based models had, on average, higher overall accuracy (0.77) than 3D point cloud‐based models (0.72). Notably, the performance was consistently >0.8 across scanning platforms and sensors, offering versatility in deployment. The top‐scoring model, DetailView, demonstrated robustness to training data imbalances and effectively generalized across tree sizes.

The FOR‐species20K dataset represents an important asset for developing and benchmarking DL models for individual tree species classification using proximally sensed laser scanning data. As such, it serves as a crucial foundation for future efforts to classify accurately and map tree species at various scales using laser scanning technology, as it provides the complete code base, dataset, and an initial baseline representative of the current state‐of‐the‐art of point cloud tree species classification methods.
Dietary Zinc Limitation Dictates Lifespan and Reproduction Trade‐Offs of Drosophila Mothers
Authors: Sarmah Sweta , Truong Hannah Thi‐Hong Hanh , McColl Gawain , Burke Richard , Mirth Christen K. , Piper Matthew D. W.
Published: February 2025

Dietary metal ions significantly influence the lifespan and reproduction of Drosophila females. In this study, we show that not adding any of the metal ions to the diet adversely affects reproduction and lifespan. By contrast, food with no added Zn negatively impacts reproduction but does not adversely affect maternal lifespan, indicating it can dictate resource reallocation between key fitness traits. Specifically, it indicates that female flies stop producing eggs to conserve their body Zn for somatic maintenance. Although these data show that flies can sense varying dietary Zn levels to adjust their physiology, they cannot maximise egg production when faced with a choice between food with no added Zn or food with sufficient Zn to support maximum reproduction. Nonetheless, they can choose to preferentially oviposit on Zn‐containing food, perhaps indicating a strategy to assure offspring survival. We also uncovered a role for the white gene in sustaining high levels of egg viability when Zn is diluted in the diet. These insights into the role of dietary metal ions, particularly Zn, point to a central role for these dietary micronutrients to indicate environmental quality and so govern trade‐offs between lifespan and reproduction in flies.