bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultradeep N-glycoproteome Atlas of Mouse Reveals Spatiotemporal Signatures of Brain Aging and Neurodegenerative Diseases
Authors: Fang Pan , Yu Xiangming , Ding MengYang , Cong Qifei , Jiang Hongyu , Shi Qi , Zhao Weiwei , Zheng Weimin , Li Yingning , Ling Zixiang , Kong WeiJun , Yang Pengyuan , Shen Huali
Published: February 2025

The current depth of site-specific N-glycoproteomics is insufficient to fully characterize glycosylation events in biological samples. Herein, we achieved an ultradeep and precision analysis of the N-glycoproteome of mouse tissues by integrating multiple workflows. The largest N-glycoproteomic dataset to date was established on mice, which contained 91,972 precursor glycopeptides, 62,216 glycoforms, 8,939 glycosites and 4,563 glycoproteins. The database consisted of 6.8 million glyco-spectra (containing oxonium ions), among which 160,928 were high-quality spectra with confident N-glycopeptide identifications. The large-scale and high-quality dataset enhanced the performance of current artificial intelligence models for glycopeptide tandem spectrum prediction. Using this ultradeep dataset, we observed tissue specific microheterogeneity and functional implications of protein glycosylation in mice. Furthermore, the region-resolved brain N-glycoproteomes for Alzheimer’s Diseases, Parkinson Disease and aging mice revealed the spatiotemporal signatures and distinct pathological functions of the N-glycoproteins. A comprehensive database resource of experimental N-glycoproteomic data from this study and previous literatures were further established. This N-glycoproteome atlas serves as a promising tool for revealing the role of protein glycosylation in biological systems.
Highly accurate prediction of broad-spectrum antiviral compounds with DeepAVC
Authors: Kang Boming , Zhao Yang , Chen Xingyu , Fan Rui , You Fuping , Cui Qinghua
Published: February 2025

Lethal viruses, such as HIV, pose a significant threat to human life, with each pandemic causing millions of fatalities globally. Small-molecule antiviral drugs provide an efficient and convenient approach to antiviral therapy by either inhibiting viral activity or activating the host immune system. However, conventional antiviral drug discovery is often labor-intensive and time-consuming due to the vast chemical space. Although some existing computational models mitigate this problem, there remains a lack of rapid and accurate method specifically designed for antiviral drug discovery. Here, we propose DeepAVC, a universal framework based on pre-trained large language models, for highly accurate broad-spectrum antiviral compounds discovery, including two models, DeepPAVC for phenotype-based prediction and DeepTAVC for target-based prediction. As a result, DeepAVC greatly outperforms otherin silicomethods. More importantly, in the top predictions, MNS and NVP-BVU972 were identified as novel compounds with promising broad-spectrum antiviral activities byin vitroexperiments. Finally, DeepAVC demonstrates high interpretability, one of the bottlenecks of current AI methods, due to its ability of analyzing key functional groups of antiviral compounds and important binding sites on targets.
Pamrevlumab did not meet its primary endpoint for non-ambulatory patients with Duchenne Muscular Dystrophy: the LELANTOS-1 trial
Authors: Connolly Anne M. , Wong Brenda L. , Phan Han C. , Mercuri Eugenio , Cai Xiaotang , Tian Cuixia , Lucia Silvana De , Nelson Stanley F. , Péréon Yann , Previtali Stefano C. , Wang Steven , Gambetti Olga V. , Brandsema John F. , Carrier Ewa
Published: February 2025

Background

In Duchenne muscular dystrophy (DMD), fibrosis is linked to connective tissue growth factor (CTGF) overexpression. Pamrevlumab, a fully human monoclonal antibody, inhibits CTGF activity and showed promise as a DMD treatment in a phase 2 trial.

Objective

LELANTOS-1 (NCT04371666) was a global phase 3 study of the safety and efficacy of pamrevlumab for non-ambulatory males ≥12 years old with DMD.

Methods

Patients were randomized 1:1 to pamrevlumab 35 mg/kg every 2 weeks for 52 weeks or placebo. All received a stable corticosteroid regimen (deflazacort or prednisone/prednisolone). Primary endpoint was total Performance of Upper Limb (PUL) v2.0 score change from baseline to Week 52 in the modified intent-to-treat (mITT) set (baseline PUL score ≥2). Treatment-emergent adverse events (TEAEs) were noted. Patients who completed the main study period were eligible to enroll in the open-label extension (OLE).

Results

Ninety-eight patients (mean [SD] age, 15.5 [2.57] years) enrolled; 48 received pamrevlumab and 49 received placebo. Between-group baseline characteristics were similar. In the mITT set (mean [SD] age, 15.5 [2.64] years; pamrevlumab, n=41; placebo, n=42), the total PUL v2.0 score change was not significantly different (p=0.8802). The pamrevlumab group had more grip strength deterioration than placebo in dominant (p=0.0161) and nondominant hands (p=0.0052). Most patients (pamrevlumab, n=45/48 [93.8%]; placebo, n=48/49 [98.0%]) experienced TEAEs (most mild/moderate). One death occurred in the pamrevlumab group (unrelated to study drug). The OLE mITT set included 72 patients. OLE efficacy and safety were consistent with the main study period. No deaths occurred during the OLE.

Conclusions

Pamrevlumab failed to meet the primary endpoint. Its future as a DMD treatment is uncertain.

Trial Registration

ClinicalTrials.gov Identifier:NCT04371666
The effectiveness of gender-based violence prevention among adolescents aged 10 to 19 years in Southeast Asia: A systematic review
Authors: Nguyen Hoa H. , To Kien G. , Hoang Van TH. , Gram Lu , Yount Kathryn M.
Published: February 2025

Background

Gender-based violence (GBV) is a major public health problem with wide-ranging negative physical and mental health consequences for survivors. The global economic costs of GBV are estimated at US$1.5 trillion. Adolescence is a period of high risk for GBV. The evidence-based GBV prevention programs among adolescents in Southeast Asia are not well understood. This paper synthesizes GBV prevention intervention studies in this region’s adolescents aged 10-19 years.

Methods

A systematic review was conducted following the PRISMA guidelines. PubMed, Medline, Embase, Web of Science, and PsycINFO were used to search for potential articles published until 3rdSeptember 2024. We screened identified articles following consistent inclusion and exclusion criteria. We assessed the risk of bias using the ROBINS-I tool for observational and quasi-experimental studies and the RoB 2 tool for randomized controlled trials.

Results

Eight of 1689 identified articles were included in the review (five quasi-experimental designs, two pre-test and post-test designs, and one cluster randomized controlled trial). Most studies (7/8) focused on school-based educational programs. The risk of bias in the cluster randomized controlled trial was “some concern” level, compared with the moderate to serious level of the non-randomized studies. One pre-and post-test study directly measured GBV behaviour and found that children reported fewer experiences of physical assault (mean difference: 1.1; 95% CI: 0.6, 1.6) and psychological aggression (1.5; 0.8, 2.3) after the intervention. The remaining studies evaluated the knowledge, attitudes, and skills of participants as primary outcomes in sexual violence prevention programs. Three of four studies that assessed changes in knowledge showed significant improvements. Inconsistent findings were found in association with attitudes and skills of GBV intervention prevention programs.

Conclusions

GBV intervention studies among adolescents in Southeast Asia are rare and evidence of effectiveness is generally weak. Rigorous RCTs that assess program impacts on GBV behaviour, as well as knowledge, attitudes, and skills, are needed. Programs that incorporate classroom activities and online learning with Facebook/Zalo/Instagram assignments and games may show promise for rigorous evaluation in Southeast Asia.

Registration

This systematic review was registered on PROSPERO (CRD42023476059).
Evidence for abstract codes in parietal cortex guiding prospective working memory
Authors: Lee Jongmin , De Vito David , Miller Jacob A. , Nee Derek Evan
Published: February 2025

The recent past helps us predict and prepare for the near future. Such preparation relies on working memory (WM) which actively maintains and manipulates information providing a temporal bridge. Numerous studies have shown that recently presented visual stimuli can be decoded from fMRI signals in visual cortex (VC) and the intra-parietal sulcus (IPS) suggesting that these areas sustain the recent past. Yet, decoding concrete, sensory signals leaves open how past information is transformed into the abstract codes critical for guiding future cognition. Here, human participants used WM to maintain a separate spatial location in each hemifield wherein locations were embedded in a star-shaped sequence. On each trial, participants made a sequence-match decision to a spatial probe and then updated their WM with the probe. The same abstract star-shaped sequence guided judgments in each hemifield allowing us to separately track concrete spatial locations (hemifield-specific) and abstract sequence positions (hemifield-general), while also tracking representation of the past (last location/position) and future (next location/position). Consistent with previous reports, concrete past locations could be decoded from VC and IPS. Moreover, in anticipation of the probe, representations shifted from past to future locations in both areas. Critically, we observed abstract coding of future sequence positions in the IPS whose magnitude related to speeded performance. These data suggest that the IPS sustains abstract codes to facilitate future preparation and reveal the transformation of the sensory past into the abstract future.
A large expert-annotated single-cell peripheral blood dataset for hematological disease diagnostics
Authors: Shetab Boushehri Sayedali , Gruber Armin , Kazeminia Salome , Matek Christian , Spiekermann Karsten , Pohlkamp Christian , Haferlach Torsten , Marr Carsten
Published: February 2025

Distinguishing cell types in peripheral blood smears is critical for diagnosing blood diseases, such as leukemia subtypes. Artificial intelligence can assist in automating cell classification. For training robust machine learning algorithms, however, large and well-annotated single-cell datasets are pivotal.

Here, we introduce a large, publicly available, annotated peripheral blood dataset comprising >40,000 single-cell images classified into 18 classes by cytomorphology experts from the Munich Leukemia Laboratory, the largest European laboratory for blood disease diagnostics. By making our dataset publicly available, we provide a valuable resource for medical and machine learning researchers and support the development of reliable and clinically relevant diagnostic tools for diagnosing hematological diseases.
Associations between residential segregation, ambient air pollution, and hippocampal features in recent trauma survivors
Authors: Liang Sophia S. , Roeckner Alyssa R. , Ely Timothy D. , Lebois Lauren A M. , van Rooij Sanne J H. , Bruce Steven E. , Jovanovic Tanja , House Stacey L. , Beaudoin Francesca L. , An Xinming , Neylan Thomas C. , Clifford Gari D. , Linnstaedt Sarah D. , Germine Laura T. , Rauch Scott L. , Haran John P. , Storrow Alan B. , Lewandowski Christopher , Musey Paul I. , Hendry Phyllis L. , Sheikh Sophia , Pascual Jose L. , Seamon Mark J. , Harris Erica , Pearson Claire , Peak David A. , Merchant Roland C. , Domeier Robert M. , Rathlev Niels K. , O’Neil Brian J. , Sergot Paulina , Sanchez Leon D. , Sheridan John F. , Harte Steven E. , Kessler Ronald C. , Koenen Karestan C. , McLean Samuel A. , Ressler Kerry J. , Stevens Jennifer S. , Webb E. Kate , Harnett Nathaniel G.
Published: February 2025

Background

Residential segregation is associated with differential exposure to air pollution. Hippocampus structure and function are highly susceptible to pollutants and associated with posttraumatic stress disorder (PTSD) development. Therefore, we investigated associations between residential segregation, air pollutants, hippocampal neurobiology, and PTSD in recent trauma survivors.

Methods

Participants (N= 278; 34% non-Hispanic white, 46% Non-Hispanic Black, 16% Hispanic) completed multimodal neuroimaging two weeks after trauma. Yearly averages of air pollutants (PM2.5and NO2) and racial/economic segregation (Index of Concentration at the Extremes) were derived from each participant’s address. Linear models assessed if air pollutants mediated associations between segregation and hippocampal volume, threat reactivity, or parahippocampal cingulum fractional anisotropy (FA) after covarying for age, sex, income, and 2-week PTSD symptoms. Further models evaluated if pollutants or segregation prospectively predicted PTSD symptoms six months post-trauma.

Results

Non-Hispanic Black participants lived in neighborhoods with significantly greater segregation and air pollution compared to Hispanic and non-Hispanic white participants (ps<.001). There was a significant indirect effect of NO2between segregation and FA values (β = 0.08, 95% CI[0.01, 0.15]), and an indirect effect of PM2.5between segregation and threat reactivity (β = -0.08, 95% CI[-0.14, -0.01]). There was no direct effect of segregation on hippocampal features. Pollutants and segregation were not associated with PTSD symptoms.

Conclusion

Residential segregation is associated with greater air pollution exposure, which is in turn associated with variability in hippocampal features among recent trauma survivors. Further research is needed to assess relationships between other environmental factors and trauma and stress-related disorders.
Disassembly of theEscherichia coliAcrABZ-TolC efflux pump by ligand-mediated disruption of TolC-AcrA interfacial contacts
Authors: Szal Tania , Petsolari Emmanouela , Veliks Janis , Cruz Cristina D. , Paunina Laura , Madre Marina , Rachad Fatima-Zahra , Lewe Philipp , Witt Susanne , Tammela Päivi , Jirgensons Aigars , Luisi Ben F. , Windshügel Björn
Published: February 2025

The outer membrane factor TolC is an essential component of various efflux pump complexes inE. coliand represents a potential target for antibiotic adjuvants. By means of a virtual screen for TolC-binding compounds, we identified the kinase inhibitor CEP- 37440 to shift the minimum inhibitory concentration of antibiotics piperacillin and levofloxacin inE. coli. To determine the substructure relevant for TolC binding, a hit deconstruction approach was applied, resulting in a fragment-like compound with low affinity for TolC and AcrB (LP-115). Dynamic light scattering revealed LP-115 to reduce the hydrodynamic radius of AcrABZ-TolC, indicating a disassembly of the efflux pump complex. A cryo-EM structure demonstrated LP-115 to bind at the TolC-AcrA interface within the AcrABZ-TolC complex, thereby disordering the interface and inducing a closed conformation of TolC. Our results suggest that ligand-mediated TolC-AcrA interface disruption represents a novel mechanism of efflux pump inhibition.
An antisense RNA regulates production of DnaA and affects sporulation inBacillus subtilis
Authors: Sedivy Emma L. , Smith Janet L. , Grossman Alan D.
Published: February 2025

DnaA is the replication initiator and a transcription factor in virtually all bacteria. Although the synthesis and activity of DnaA are highly regulated, the mechanisms of regulation vary between organisms. We found that production of DnaA inBacillus subtilisis regulated by an antisense RNA that overlaps with the 5’ untranslated region upstream of thednaAopen reading frame. We initially observed this RNA in in vitro transcription experiments and found that its production was inhibited by DnaA. This RNA, now called ArrA forantisenseRNArepressor ofdnaA, is made in vivo. We identified thearrApromoter and made a mutation that greatly reduced (or eliminated) production of ArrA RNA in vitro and in vivo. In vivo, thisarrApromoter mutation caused an increase in the amount of mRNA and protein fromdnaAanddnaN, indicating thatarrAexpression normally inhibits expression of thednaA-dnaNoperon. ThearrAmutation also caused a delay in sporulation that was alleviated by loss ofsda, a sporulation-inhibitory gene that is directly activated by DnaA.arrAappears to be conserved in some members of theBacillusgenus, indicating thatarrAhas evolved in at least some endospore-forming bacteria to modulate production of DnaA and enable timely and robust sporulation.

Author summary

DnaA is the highly conserved replication initiator and transcription factor found in virtually all bacteria. The synthesis and activity of DnaA are highly regulated, and different types of bacteria use different mechanisms to control this key protein. We found that DnaA production inBacillus subtilisis inhibited by an antisense RNA that overlaps with the 5’ untranslated region of thednaAmRNA. In the absence of this antisense RNA, there was an increase in the amount ofdnaAmRNA and protein. There was also a delay in sporulation that depends onsda, a sporulation-inhibitory gene that is directly activated by DnaA.arrAappears to be conserved in several members of theBacillusgenus, indicating that it has evolved to temper production DnaA and enable robust sporulation in these species.
A novelLeishmania infantumreference strain for gene editing and the study of visceral leishmaniasis
Authors: Thiam Rokhaya , Ceballos Maria Santana , Beneke Tom , Kuk Nada , Pasquier Grégoire , Crobu Lucien , Jeffares Daniel C , Vergnes Baptiste , Barckmann Bridlin , Sterkers Yvon
Published: February 2025

Parasites of theLeishmania donovanicomplex are responsible for visceral leishmaniasis, a vector-borne disease transmitted through the bite of female phlebotomine sand flies. As well as the human hosts, these parasites infect many mammals which can serve as reservoirs. Dogs are particularly important reservoirs in Europe. Transmission is widespread across Asia, Africa, the Americas, and the Mediterranean basin, including South of France. Visceral leishmaniasis poses a fatal threat if left untreated. Research into the pathophysiology of this neglected disease is of prime importance, as is the development of new drugs. In this study, we evaluated the growth, differentiation, and macrophage infectivity of fourL. donovanicomplex strains and identifiedL. infantumS9F1 (MHOM/MA/67/ITMAP263, clone S9F1) as a well-adapted strain for genetic engineering studies. We present here the genome sequence and annotation ofL infantumS9F1 T7 Cas9, providing the scientific community with easy access to its genomic information. The data has been integrated into the LeishGEdit online resource to support primer design for CRISPR-Cas9 experiments. We now aim to make this strain widely available to foster pathogenesis studies of visceral leishmaniasis.

AUTHOR SUMMARY

Visceral leishmaniasis is a disease caused by parasites of theLeishmania donovanicomplex. These parasites are spread to humans and animals through the bites of sand flies, and this disease affects millions of people worldwide, particularly in regions such as the Americas, Asia, Africa, and the Mediterranean basin. If left untreated, it can be fatal. Researchers need to study the biology of the parasite that causes the disease to better understand how it develops and progresses. In this study, we identified aL. infantumstrain that is amenable to genetic modification in the laboratory and may serve as a representative model of the causative agent of visceral leishmaniasis. We tested two CRISPR-Cas9 strategies on this strain, re-sequenced and annotated its genome, and made the data available on the LeishGEdit website. By sharing this strain with the research community, we aim to support further studies on the pathogenesis of visceral leishmaniasis.
The small GTPase Rab5 inhibits actin polymerization mediated by theLegionella pneumophilaeffector VipA
Authors: Saraiva Joana , Bugalhão Joana N. , Carvalho Teresa , Hensel Zach , Crevenna Alvaro , Mota L. Jaime , Franco Irina S.
Published: February 2025

Legionella pneumophilais a facultative intracellular Gram-negative bacterium that causes Legionnaires’ disease, one of the most severe manifestations of atypical pneumonia.L. pneumophilanaturally thrives within protozoan hosts in aquatic environments, which serve as reservoirs for bacterial replication and transmission. Inhalation of contaminated aerosols deliversL. pneumophilato the lungs where it is able to infect human alveolar macrophages and multiply intracellularly inside a membrane-bound compartment, theLegionella-containing vacuole (LCV). The main virulence factor of the bacteria is the Icm/Dot type IVb secretion system, responsible for the translocation of over 300 bacterial effector proteins into host cells. These effectors allow the remodelation of the LCV into a replication-competent compartment that seggregates from the phagolysosomal pathway.

After being translocated into host cells,L. pneumophilaeffector VipA associates with early endosomes and F-actin. VipA increases the polymerization of actin filamentsin vitroby promoting the nucleation step without the requirement of additional partners, and impairs vesicle trafficking inSaccharomyces cerevisiae. In this work, we sought the interacting partners of VipA in early endosomes and explored the effects of this association. We found that VipA interacts directly to two key components of these organelles, the membrane lipid PI3P and the small GTPase Rab5. Binding to Rab5 requires the N-terminal region of VipA but not the C-terminal/actin-binding region. Furthermore, binding to Rab5 inhibits VipA-mediated actin polymerization by preventingde novoactin filament formation. These findings offer new insights into VipA’s mode of action and underscore the intricate interactions betweenL. pneumophilaeffectors and their host cell targets, namely the endocytic pathway.
Chronic social defeat causes dysregulation of systemic glucose metabolism via the cerebellar fastigial nucleus
Authors: Ishimoto Taiga , Abe Takashi , Nakamura Yuko , Tsuyama Tomonori , Kondoh Kunio , Kajitani Naoto , Yoshida Kaede , Takeuchi Yuichi , Kato Kan X. , Xu Shucheng , Koduki Maru , Ichimura Momoka , Itoi Takito , Shimba Kenta , Yamaguchi Yoshifumi , Minami Masabumi , Koike Shinsuke , Kasai Kiyoto , Ye Jessica J , Takebayashi Minoru , Yamagata Kazuya , Toda Chitoku
Published: February 2025

Chronic psychological stress leads to hyperglycemia through the endocrine and sympathetic nervous systems, which contributes to the development of type II diabetes mellitus (T2DM). Higher plasma corticosteroids after stress is one well-established driver of insulin resistance in peripheral tissues. However, previous studies have indicated that only a fraction of patients with depression and post-traumatic disorder (PTSD) who develop T2DM exhibit hypocortisolism, so corticosteroids do not fully explain psychological stress-induced T2DM. Here, we find that chronic social defeat stress (CSDS) in mice enhances gluconeogenesis, which is accompanied by a decrease in plasma insulin, an increase in plasma catecholamines, and a drop in plasma corticosterone levels. We further reveal that these metabolic and endocrinological changes are mediated by the activation of neurons projecting from the cerebellar fastigial nucleus (FN) to the medullary parasolitary nucleus (PSol). These neurons are crucial in shifting the body’s primary energy source from glucose to lipids. Additionally, data from patients with depression reveal correlations between the presence of cerebellar abnormalities and both worsening depressive symptoms and elevated HbA1c levels. These findings highlight a previously unappreciated role of the cerebellum in metabolic regulation and its importance as a potential therapeutic target in depression, PTSD, and similar psychological disorders.
Altered auditory feature discrimination in a rat model of Fragile X Syndrome
Authors: Walker Gauthier D. , James Noelle , Auerbach Benjamin D.
Published: February 2025

Atypical sensory processing, particularly in the auditory domain, is one of the most common and quality-of-life affecting symptoms seen in autism spectrum disorders (ASD). Fragile X Syndrome (FXS) is the leading inherited cause of ASD and a majority of FXS individuals present with auditory processing alterations. While auditory hypersensitivity is a common phenotype observed in FXS andFmr1KO rodent models, it is important to consider other auditory coding impairments that could contribute to sound processing difficulties and disrupted language comprehension in FXS. We have shown previously that aFmr1knockout (KO) rat model of FXS exhibits heightened sound sensitivity that coincided with abnormal perceptual integration of sound bandwidth, indicative of altered spectral processing. Frequency discrimination is a fundamental aspect of sound encoding that is important for a range of auditory processes, such as source segregation and speech comprehension, and disrupted frequency coding could thus contribute to a range of auditory issues in FXS and ASD. Here we explicitly characterized spectral processing deficits in maleFmr1KO rats using an operant conditioning tone discrimination assay andin vivoelectrophysiology recordings from the auditory cortex and inferior colliculus. We found thatFmr1KO rats exhibited poorer frequency resolution, which corresponded with neuronal hyperactivity and broader frequency tuning in auditory cortical but not collicular neurons. Using an experimentally informed population model, we show that these cortical physiological differences can recapitulate the observed behavior discrimination deficits, with decoder performance being tightly linked to differences in cortical tuning width and signal-to-noise ratios. These findings suggest that cortical hyperexcitability may account for a range of auditory behavioral phenotypes in FXS, providing a potential locus for development of novel biomarkers and treatment strategies that could extend to other forms of ASD.
A single-cell transcriptomic atlas of developing inhibitory neurons reveals expanding and contracting modes of diversification
Authors: Micoli Elia , Ferrero Restelli Facundo , Barbiera Giulia , Moors Rani , Nouboers Evelien , Du Jessica Xinyun , Bertels Hannah , Liu Minhui , Konstantopoulos Dimitris , Takeoka Aya , Lippi Giordiano , Lim Lynette
Published: February 2025

The cerebral cortex relies on vastly different types of inhibitory neurons to compute. How this diversity emerges during development remains an open question. The rarity of individual inhibitory neuron types often leads to their underrepresentation in single-cell RNA sequencing (scRNAseq) datasets, limiting insights into their developmental trajectories. To address this problem, we developed a computational pipeline to enrich and integrate rare cell types across multiple datasets. Applying this approach to somatostatin-expressing (SST+) inhibitory neurons—the most diverse inhibitory cell class in the cortex—we constructed the Dev-SST-Atlas, a comprehensive resource containing mouse transcriptomic data of over 51,000 SST+ neurons. We identify three principal groups—Martinotti cells (MCs), non-Martinotti cells (nMCs), and long-range projecting neurons (LRPs)—each following distinct diversification trajectories. MCs commit early, with distinct embryonic and neonatal clusters that map directly to adult counterparts. In contrast, nMCs diversify gradually, with each developmental cluster giving rise to multiple adult cell types. LRPs follow a unique ‘contracting’ mode. Initially, two clusters are present until postnatal day 5 (P5), but by P7, one type is eliminated through programmed cell death, leaving a single surviving population. This transient LRP type is also found in the fetal human cortex, revealing an evolutionarily conserved feature of cortical development. Together, these findings highlight three distinct modes of SST+ neuron diversification—invariant, expanding, and contracting—offering a new framework to understand how the large repertoire of inhibitory neurons emerges during development.
White-matter controllability at birth predicts social engagement and language outcomes in toddlerhood
Authors: Sun Huili , Vernetti Angelina , Spann Marisa , Chawarska Katarzyna , Ment Laura , Scheinost Dustin
Published: February 2025

Social engagement and language are connected through early development. Alterations in their development can have a prolonged impact on children’s lives. However, the role of white matter at birth in this ongoing connection is less well-known. Here, we investigate how white matter at birth jointly supports social engagement and language outcomes in 642 infants. We use edge-centric network control theory to quantify edge controllability, or the ability of white-matter connections to drive transitions between diverse brain states, at 1 month. Next, we used connectome-based predictive modeling (CPM) to predict the Quantitative Checklist for Autism in Toddlers (Q-CHAT) for social engagement risks and the Bayley Scales of Infant and Toddler Development (BSID-III) for language skills at 18 months from edge controllability. We created the social engagement network (SEN) to predict Q-CHAT scores and the language network (LAN) to predict BSID-III scores. The SEN and LAN were complex, spanning the whole brain. They also significantly overlapped in anatomy and generalized across measures. Controllability in the SEN at 1 month partially mediated associations between Q-CHAT and BSID-III language scores at 18 months. Further, controllability in the SEN significantly differed between term and preterm infants and predicted Q-CHAT scores in an external sample of preterm infants. Together, our results suggest that the intertwined nature of social engagement and language development is rooted in an infant’s white-matter controllability.

Significance Statement

During infancy and toddlerhood, social engagement and language emerge together. Delays are often observed in both simultaneously. These interactions persist into later childhood, potentially affecting life quality. We reveal that the interplay between social engagement and language milestones in toddlerhood is rooted in the infant’s structural connectivity, which may assist in early risk identification of developmental delays. Insights into the early brain foundations for emerging social engagement and language skills may open opportunities for individualized interventions to improve developmental outcomes.
On the typical development of the central sulcus in infancy: a longitudinal evaluation of its morphology and link to behaviour
Authors: Dornier Amaia , Gérard Alexia , Leprince Yann , Hertz-Pannier Lucie , Mangin Jean-François , Barbu-Roth Marianne , Dubois Jessica , Muret Dollyane
Published: February 2025

Introduction

The progressive folding of the cortex is an important feature of neurodevelopment starting early during gestation. The central sulcus (CS) is one of the first to fold. Since it represents the anatomical boundary between primary somatosensory and motor functional regions, its developing morphology may inform on the acquisition of sensorimotor skills. We aimed to identify potential asynchronous morphological changes along the CS during infancy, with the hypothesis that this may reflect the gradual emergence of body usage.

Method

Based on 3T anatomical magnetic resonance imaging (MRI) and dedicated post-processing, we characterized the evolution in CS depth and curvature in 33 typical infants (aged 1 and 3 months, 22 with longitudinal data) in relation to 23 young adults as a reference. Four regions of interest (ROIs) along the CS, supposed to correspond to different parts of the body and one centred on the hand knob (HK), were reproducibly examined and compared across groups. We also explored the relationship between the age-related changes in morphological features and the global motor scaled scores evaluated at 3 months of age with the Bayley Scales of Infant and Toddler Development.

Results

While all ROIs showed significant increases in CS depth and curvature between 3-month-olds and adults, the results were more variable between 1 and 3 months of age depending on cross-sectional and longitudinal analyses. The central-medial and central-lateral regions showed the most consistent increase in depth. Besides, motor development at 3 months of age was not significantly related to CS morphological changes, but a positive trend was observed for depth changes in the (HK-related) central-medial ROI.

Conclusion

The rapid evolution of CS folding during infancy may reflect the intense but asynchronous maturation of the brain sensorimotor system, with the differential growth of cortical areas related to body parts and underlying white matter connections. Although it will have to be replicated on larger groups and at other ages, this longitudinal and multimodal study highlights the potential of characterizing CS features as key markers of early sensorimotor development, both at the cerebral and behavioural levels. Combining anatomical and functional neuroimaging could provide deeper insights into the relationship between CS morphology and somatotopic organization in typical infants, but also in infants at risk of developing motor disorders.
Influenza A Virus Interferes With Respiratory Syncytial Virus in Mice and Reconstituted Human Airway Epithelium
Authors: Gilbert-Girard Shella , Piret Jocelyne , Rhéaume Chantal , Carbonneau Julie , Goyette Nathalie , Couture Christian , Boivin Guy
Published: February 2025

Epidemiological studies suggest that respiratory syncytial virus (RSV) and influenza A virus (IAV) might interfere with each other. Viral interference mainly relies on interferon production elicited by a first virus that reduces the replication of a second virus. In this paper, we first investigated the interactions between RSV-A2 and influenza A(H1N1)pdm09 in BALB/c mice infected with each single virus or both viruses simultaneously or sequentially before, at the peak of interferon elicited by each virus or after that peak. IAV reduced by almost 3.0 logs the replication of RSV administered at the peak of interferon induced by influenza, but the opposite was not true. However, IAV-infected mice challenged with RSV or the vehicle lost more weight and had a lower survival rate compared to single infections. Interferon expression, cytokine levels and pulmonary inflammation were almost similar between groups. Disease worsening was attributed to an aggravation of IAV-induced pulmonary congestion following intranasal instillation of fluid (with or without RSV). In human airway epithelia, IAV also interfered with RSV replication. Viral interference was dependent on the timing and sequence of infections, but not on differential interferon susceptibilities. Overall, our results help to understand the mechanisms of interaction between two major respiratory viruses.

Importance

Respiratory syncytial virus and influenza virus may interfere with each other based on epidemiological studies. It is suggested that a first virus may induce the production of interferon and interfere with the replication of a second unrelated virus. Our data showed that influenza A virus interferes with respiratory syncytial virus replication in mouse lungs, but the opposite was not observed. In reconstituted human airway epithelia, viral interference was dependent on the timing and sequence of infections, but not on differential interferon susceptibilities. Understanding the mechanisms of interaction between respiratory viruses may help the development of prophylactic or therapeutic modalities.
Type-II topological phase transitions of topological skyrmion phases
Authors: Ay Reyhan , Winter Joe H. , Cook A. M.
Published: February 2025

We present minimal toy models for topological skyrmion phases of matter, which generically realize type-II topological phase transitions in effectively noninteracting systems, those which occur without closing of the minimum direct bulk energy gap. We study the bulk-boundary correspondence in detail to show that a nontrivial skyrmion number yields a rich bulk-boundary correspondence. We observe gapless edge states, which are robust against disorder, due to nontrivial skyrmion number. Edge states corresponds to bands, which do not traverse the bulk gap, instead yielding gaplessness due to their overlap in energy and exponential localization on opposite edges of the system. These gapless boundary modes can occur for total Chern number zero, and furthermore correspond to rich real-space spin textures with strong polarization of spin along the real-space edge. By introducing toy models generically exhibiting type-II topological phase transitions and characterizing the bulk-boundary correspondence due to nontrivial skyrmion number in these models, we lay the groundwork for understanding consequences of the quantum skyrmion Hall effect.

Published by the American Physical Society
2025
Analysis of
π0
,
KS0
, and
η
fragmentation functions using single-inclusive annihilation data including BESIII measurements
Authors: Li Mengyang , Anderle Daniele Paolo , Xing Hongxi , Zhao Yuxiang
Published: February 2025

This study presents a quantum chromodynamics (QCD) analysis of fragmentation functions (FFs) for neutral pions (π0), neutral kaons (KS0), and eta mesons (η), utilizing world data of single-inclusive hadron production in e+e− annihilation involving the most recent BESIII data with low collision energy, to test the operational region of QCD collinear factorization for single-inclusive hadron production. We found that the QCD-based analysis at next-to-next-to-leading order in perturbative QCD with parametrized higher-twist effects can explain both existing high-energy world data and the BESIII new measurements, while the latter cannot be explained with existing FFs extracted with high-energy data. To investigate the higher-twist contributions to this discrepancy, a direct functional approach is employed, providing a testing framework for characterizing the experimental results over a wide range of energy scales, from low to high, thus extending the classical theoretical models to the BESIII domain.

Published by the American Physical Society
2025
Color superconductivity and speed of sound in the two-flavor quark-meson diquark model
Authors: Andersen Jens O. , Nødtvedt Mathias P.
Published: February 2025

We discuss the properties of the two-flavor quark-meson diquark (QMD) model as a renormalizable low-energy model for quantum chromodynamics (QCD) in the 2SC phase of QCD. The effective degrees of freedom are the mesons (sigma and pions), quarks, and diquarks. Some of the parameters of the model can be determined by expressing them in terms of the vacuum meson masses and the pion decay constant using the on-shell renormalization scheme. The remaining parameters are considered free, although they in principle can be calculated from QCD. The thermodynamic potential is calculated in a mean-field approximation taking only quark loops into account. In this approximation, we derive a set of renormalization group equations for the running masses and couplings. The solutions to these equations are used to improve the thermodynamic potential Ω and thereby thermodynamic quantities. Four parameter sets are chosen and the phase diagram in the μ¯−T plane is obtained (with μ¯=13μB). We also calculate the speed of sound cs as a function of μ¯ at vanishing temperature. For large values of μ¯, the speed of sound approaches the conformal limit cs=13 from above, in disagreement with perturbative calculations, but in agreement with hard-dense-loop resummed perturbation theory.

Published by the American Physical Society
2025
Energy-preserving coupling of explicit particle-in-cell with Monte Carlo collisions
Authors: Vay Jean-Luc , Angus Justin Ray , Shapoval Olga , Lehe Rémi , Grote David , Huebl Axel
Published: February 2025

The particle-in-cell (PIC) and Monte Carlo collisions (MCC) methods are workhorses of many numerical simulations of physical systems. Recently, it was pointed out that, while the two methods can be exactly—or nearly—energy-conserving independently, combining the two leads to anomalous numerical heating. This paper reviews the standard explicit PIC-MCC algorithm, elucidates the origins of the anomalous numerical heating, and explains how to couple the two methods such that the anomalous numerical heating is avoided.

Published by the American Physical Society
2025
Transverse Force Distributions in the Proton from Lattice QCD
Authors: Crawford J. A. , Can K. U. , Horsley R. , Rakow P. E. L , Schierholz G. , Stüben H. , Young R. D. , Zanotti J. M. ,   QCDSF Collaboration
Published: February 2025

Single-spin asymmetries observed in polarized deep-inelastic scattering are important probes of hadron structure. The Sivers asymmetry has been the focus of much attention in QCD phenomenology and is yet to be understood at the quark level. In this Letter, we present a lattice QCD calculation of the spatial distribution of a color-Lorentz force acting on the struck quark in a proton. We determine a spin-independent confining force, as well as spin-dependent force distributions with local forces on the order of 3  GeV/fm. These distributions offer a complementary picture of the Sivers asymmetry in transversely polarized deep-inelastic scattering.

Published by the American Physical Society
2025
Light
Λ
Hypernuclei Studied with Chiral Hyperon-Nucleon and Hyperon-Nucleon-Nucleon Forces
Authors: Le Hoai , Haidenbauer Johann , Meißner Ulf-G. , Nogga Andreas
Published: February 2025

A study of light Λ hypernuclei in chiral effective field theory is presented. For the first time, chiral ΛNN and ΣNN three-body forces are included consistently. The calculations are performed within the no-core shell model. Results for the separation energies of the hypernuclei HΛ3, HΛ4/HeΛ4, HeΛ5, and LiΛ7 are given. It is found that the experimental values can be fairly well reproduced once hyperon-nucleon-nucleon three-body forces are taken into account.

Published by the American Physical Society
2025
Constant-Current Nonequilibrium Molecular Dynamics Approach for Accelerated Computation of Ionic Conductivity Including Ion-Ion Correlation
Authors: Sasaki Ryoma , Tateyama Yoshitaka , Searles Debra J.
Published: February 2025

Calculation of ionic conductivity including ion-ion correlation effects using equilibrium molecular dynamics (EMD) is computationally demanding, but the correlation is significant in many promising electrolytes such as solid electrolytes. Herein, we have developed a “constant-current” nonequilibrium MD (NEMD) simulation method, in contrast to the conventional constant-field approach, for ion-ion correlated conductivities from a constrained ionic current with fluctuating external field. The improved efficiency of the constant-current NEMD approach is demonstrated by applying it to a representative solid electrolyte, cubic Li7La3Zr2O12. The convergence of the correlated conductivity is faster than that of EMD by 2 orders of magnitude. The low-temperature NEMD simulations also reveal that the ionic conductivity of Li7La3Zr2O12 exhibits non-Arrhenius behavior of the activation energy that changes at around 600 K. This work presents not only the high sampling efficiency of constant-current NEMD to calculate the correlated ionic conductivity, but also the importance of direct computations of ionic conductivity at low temperature without Arrhenius extrapolation.

Published by the American Physical Society
2025
Implications of rapid changes and identity transformation on walkability in Heliopolis, Cairo, Egypt
Authors: Amgad Mahmoud , Galal Omar Mohamed , Wanas Ayman
Published: February 2025

Purpose

Investigating the effects of rapid urban changes and identity changes on walkability in the Heliopolis area is the aim of this study. The study attempts to evaluate how these changes impact pedestrian movement and the general walkability of urban spaces by examining streets and squares that have either retained or lost their original identity as a result of modifications favoring private vehicles. This research aims to highlight the importance of maintaining urban identity and other contributing variables in fostering walkable, livable settings through a comparative analysis using various methodologies such as walking tours, observations and interviews.

Design/methodology/approach

This study uses a mixed-method approach to examine the relationship between walkability and urban identity in Heliopolis by integrating subjective and objective strategies. Only one of the four squares and four streets that were chosen kept its original status. A comparison study was carried out between the altered and conserved sites. The techniques included documenting changes in the built environment, walking assessment tours, and on-site observations. Seven semi-structured interviews and fifty photographic attitude surveys were also carried out. The effects of urban changes on walkability were then evaluated by correlating and mapping the data.

Findings

The study discovered a significant relationship in Heliopolis between improved walkability and the maintenance of urban identity. Streets and squares that preserved their identity offered greater pedestrian experiences and had higher walkability ratings. On the other hand, areas that experienced changes that favored private vehicles demonstrated decreased comfort for pedestrians and decreased walkability. But the study also showed that walkability is highly influenced by non-identity-related characteristics like how ground-floor spaces are used. The findings imply that while walkability is greatly enhanced by urban identity, better pedestrian environments require a comprehensive strategy that addresses a variety of urban design components.

Originality/value

By examining the relationship between walkability, identity transition and quick urban shifts in a historic area like Heliopolis, this study makes a distinctive contribution. This research emphasizes the frequently underappreciated significance of urban identity in influencing pedestrian experiences, in contrast to earlier studies that only focused on physical infrastructure or urban architecture. Using a mixed-method approach that includes interviews, maps and visual surveys, it offers a thorough examination of how changes—especially those that favor private vehicles—affect walkability. The results provide insightful information on the significance of maintaining urban identity in conjunction with other design components to improve walkable settings for urban planners and policymakers.