bluuebunny/crossref_metadata_2025 huggingface dataset:
Soft-Tissue Metastases on FDG-PET in Advanced Prostate Cancer
Authors: Dawson Debra Ann , Rachinsky Irina
Published: February 2025

An 80-year-old man was found to have metastatic prostate carcinoma at the initial diagnosis. CT imaging revealed multiple large soft tissue masses in the neck, lungs, hila, mediastinum, retroperitoneum, peritoneum, and axillae, as well as multifocal bony lesions. An FDG-PET/CT was ordered to help clarify whether the thoracic findings were likely attributable to a synchronous lung malignancy. FDG-PET/CT images showed hypermetabolic soft tissue lesions, lymphadenopathy above and below the diaphragm, a left perihilar mass, and multiple skeletal metastases. Since the observed lesions showed similar metabolic activity as a biopsy-proven prostate metastasis, all metastatic involvement was favored secondary to prostate cancer.
Movement System Diagnosis: A Consensus-Based Position for Pediatric Movement Specialists
Authors: Cobb Lorene P , Shane Kelly Ann , McGee Patricia Navarro , Nesbit Casey , Brennan Ellen , Moore Jim , Girolami Gay L , Dannemiller Lisa , Donaldson Cathron , Boynewics Kara , Carey Helen , Chase Kristine Michelle , Hall Amanda , Jones Maryleen , O’Shea Roberta Kuchler , Zipp Genevieve Pinto
Published: February 2025

Purpose:

To offer a consensus for pediatrics clinicians, educators, and researchers on the use of movement system (MS) and review evidence that supports physical therapists (PTs) as movement experts.

Summary of Key Points:

This paper describes the MS and discusses how a MS diagnosis (Dx) can lead to most effective interventions and plans of care (POC) in pediatrics. Three cases illustrate using organized formulation of MS Dxs and how a MS Dx assists in choosing affective interventions for the POC.

Conclusions:

Pediatric PTs are movement specialists designing individualized plans of care to meet functional goals in real world conditions. Using consistent terms to establish MS Dx will enable effective communication, and a foundation for interventions across the lifespan.

Recommendations:

Adopting MS Dx framework will support and assist students of physical therapy, entry level and experienced clinicians, educators, and researchers with a critical decision-making process for formulating optimal family centered care.
Disability Inclusion in Local Public Health Community Health Assessments and Community Health Improvement Plans
Authors: Leslie Haleigh , Beatty Kate , Rowe Dawn , Quade Thomas , Havrda Kailee , Balio Casey P.
Published: February 2025

Objective:

To quantify and describe disability inclusion in community health assessments (CHAs) and community health improvement plans (CHIPs) at the local health department (LHD) level.

Methods:

This study uses a cross-sectional design of the 2019 NACCHO Profile and Public Health Accreditation Board-accredited LHD CHAs and CHIPs to quantify and describe disability inclusion.

Results:

Less than 25% of LHDs included a CHIP goal, objective, or activity that specifically includes people with disabilities. Having a disability partner as part of CHA and CHIP steering committees was associated with greater odds of including a CHIP goal, objective, or activity that includes people with disabilities (adjusted odds ratio (aOR) = 3.2, P =<.01) as were CHAs and CHIPs conducted by mixed groups of community partners (but not an official coalition) (aOR = 5.04, P = .005).

Conclusions:

Given the role of CHAs and CHIPs in informing the work of public health, being disability inclusive in such materials is likely to reflect the activities of LHDs. However, disability inclusion and representation in CHAs and CHIPs are limited. These findings may help inform CHA and CHIP development processes and tools to increase disability inclusion efforts in public health.
Variability in the Implementation of Best Practices for Sexual Assault Case Handling Across US Law Enforcement and Prosecutorial Agencies
Authors: Gonzalez Veronica Valencia
Published: February 2025

This brief report examines variability in the implementation of best practices for handling sexual assault cases across US law enforcement and prosecutorial agencies. Despite national guidelines promoting trauma-informed interviewing, timely forensic evidence collection, and collaborative interagency work, adoption varies widely. Surveys from 362 agencies and interviews with 25 representatives indicate that larger, metropolitan agencies are more likely to establish specialized units and incorporate victim advocates early in the process. In contrast, smaller and rural agencies report significant barriers, such as limited resources, lack of specialized training, and inconsistent collaboration. This variability underscores a critical need for more standardized guidelines to ensure uniform, survivor-centered approaches across jurisdictions. Addressing these disparities could improve outcomes for sexual assault survivors by promoting equity in care provision across diverse community settings. Additionally, addressing survivors’ sexual health needs, including the identification, prophylaxis, and treatment of sexually transmitted infections, is critical to comprehensive care.
Update on Dupuytren Disease: Pathogenesis, Natural History, Treatment, and Outcomes
Authors: Ohmes Lucas B. , Ghilzai Umar M. , Netscher David T. J.
Published: February 2025

Learning Objectives:

After studying this article, the participant should be able to: 1. Understand the current molecular biology of Dupuytren disease. 2. Critically evaluate the functional outcomes of treatment. 3. Confidently use any of the commonly used treatments. 4. Provide patients with appropriately selected treatment choices.

Dupuytren disease is a fibroproliferative disease of the palmar fascia that results in debilitating digital contractures. Despite medical advances, the measurement of disease severity, functional deficits, and treatment outcomes remains challenging. Treatment options vary widely, yet practitioners often use only a small number of modalities. These options range from minimally invasive office procedures to extensive surgery, with adjuncts such as radiation and soft-tissue flaps. A thorough understanding of disease pathophysiology and treatment options can help surgeons offer more individualized care for this elusive disease.
Outcomes following prenatal exposure to raltegravir-containing antiretroviral therapy: a multi-cohort European study
Authors: Sconza Rebecca , Fernandes. Georgina , Bailey Heather , Peters Helen , Prieto Tato Luis Manuel , Ramos Marta Illán , Aebi-Popp Karoline , Kahlert Christian , Gamell Anna Maria , Frick Antoinette , Ene Luminita , Samarina Anna , Thorne Claire ,   European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)
Published: February 2025

Background:

Raltegravir is an HIV integrase strand transfer inhibitor recommended for use in pregnancy. The aim of this study was to assess risk of birth defects and other suboptimal outcomes following prenatal exposure to raltegravir.

Methods:

We used pooled, prospectively-collected individual patient data from studies in the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC). Pregnancies with any prenatal exposure to raltegravir with outcomes in 2008-2020 were included. Birth defects were classified according to World Health Organization’s International Classification of Diseases: Tenth Revision (ICD-10) and EUROCAT criteria. Earliest prenatal exposure timing was classified as periconception (exposure at ≤6 completed gestational weeks [GWs]), later first trimester (T1) (exposure in T1 at >6 completed GWs), and second/third trimester (exposure at >12 completed GWs).

Results:

A total of 1499 pregnancies across nine cohorts were included. Where timing was available (n=1449), earliest raltegravir exposure was in the periconception period for 505 (34.8%), later T1 in 65 (4.5%), and T2/T3 in 879 (60.7%). The overall prevalence of birth defects among live-born infants with prenatal raltegravir exposure was 3.9% (95% CI 2.9, 5.0) (1443/1466) (ICD-10), with no increased risk observed for those exposed in the periconception period (p=0.290). Among singleton live-born infants, 11.9% (160/1346) were born preterm, 11.3% (148/1307) low birthweight, and 8.6% (111/1291) small for gestational age, with no difference in outcomes observed by timing of raltegravir exposure.

Conclusion:

These findings add to the evidence base around safety of raltegravir use in pregnancy, though ongoing safety monitoring is needed to rule out risk of rare outcomes.
Validation of the ANCA-Associated Vasculitis Patient-Reported Outcomes Questionnaire in a Latin American Vasculitis Cohort
Authors: Pimentel-Quiroz Victor R. , Gamboa-Cárdenas Rocío V. , Rodríguez-Bellido Zoila , Perich-Campos Risto , Alarcón Graciela S. , Ugarte-Gil Manuel F.
Published: February 2025

Background/Objectives

The aim of this work is to validate the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire in a Latin American (Peru) AAV cohort.

Methods

We included patients from the Almenara vasculitis cohort who had at least 1 visit between December 2022 and June 2024. Sociodemographic features, disease activity (Birmingham Vasculitis Activity Score version 3 [BVASv3] score), damage (Vasculitis Damage Index [VDI] score), the AAV-PRO (Spanish version), and the Short Form 36 (SF-36) were obtained. The AAV-PRO includes 6 domains (organ-specific symptoms, systemic symptoms, treatment side effects, social and emotional impact, concerns about the future, and physical function); the score ranges from 0 to 100: the higher the value, the worse the health-related quality of life. Correlations between domains of the AAV-PRO and clinical and sociodemographic variables were evaluated using Spearman correlation.

Results

Eighty-two patients were included; 60 (73.2%) of them were female. Their age and disease duration were 55.3 (14.3) and 5.7 (5.2) years, respectively. The BVASv3 and the VDI scores were 6.1 (9.0) and 2.4 (1.7), respectively. Overall, every domain of the AAV-PRO correlated strongly and inversely with the global scores of the SF-36 (physical component summary and mental component summary) (all r < −0.4 and p < 0.001). Physical function, role physical, role emotional, and physical component summary correlated inversely with the BVASv3, whereas the organ-specific symptoms score correlated positively with the VDI.

Conclusions

The Spanish version of the AAV-PRO questionnaire correlated with the SF-36 in AAV patients from a Peruvian cohort. These findings may support the use of this instrument in other Latin American populations.
Integrated Ultrasound Neuromodulation and Optical Neuroimaging in Awake Mice using a Transparent Ultrasound Transducer Cranial Window
Authors: Mirg Shubham , Samanta Krishnendu , Chen Haoyang , Jiang Jin , Turner Kevin L. , Salehi Fatemeh , Ramiah Kathiravan M. , Drew Patrick J. , Kothapalli Sri-Rajasekhar
Published: February 2025

Ultrasound neuromodulation is a rapidly advancing, non-invasive technique with significant therapeutic potential for treating various neurological disorders. Although extensive in vitro and in vivo studies have provided valuable insights into its modulatory effects, the underlying mechanisms remain poorly understood, limiting its clinical translation. Optical neuroimaging techniques can help investigate these mechanisms; however, the opacity and bulkiness of conventional ultrasound transducers pose significant challenges for their integration with in vivo ultrasound neuromodulation studies, particularly in awake rodents. To address these limitations, we propose a straightforward solution: a miniaturized lithium niobate-based transparent ultrasound transducer (TUT) integrated as a thinned-skull cranial window for ultrasound stimulation while facilitating multimodal optical neuroimaging in awake mice brain. Using laser speckle contrast imaging and intrinsic optical signal imaging, we studied changes in brain hemodynamics in response to various ultrasound stimulation sequences. Our experiments demonstrated that TUT cranial window can robustly induce neuromodulatory effects with observed increase in both cerebral blood flow and total hemoglobin, with peak and cumulative hemodynamic changes directionally correlated with ultrasound stimulation duration and intensity. Overall, these findings highlight that TUT cranial window can seamlessly integrate ultrasound stimulation and optical neuroimaging in awake mouse brain models, offering promising prospects for uncovering the underlying mechanisms of ultrasound neuromodulation.
Lab-in-the-loop therapeutic antibody design with deep learning
Authors: Frey Nathan C. , Hötzel Isidro , Stanton Samuel D. , Kelly Ryan , Alberstein Robert G. , Makowski Emily , Martinkus Karolis , Berenberg Daniel , Bevers Jack , Bryson Tyler , Chan Pamela , Czubaty Alicja , D’Souza Tamica , Dwyer Henri , Dziewulska Anna , Fairman James W. , Goodman Allen , Hofmann Jennifer , Isaacson Henry , Ismail Aya , James Samantha , Joren Taylor , Kelow Simon , Kiefer James R. , Kirchmeyer Matthieu , Kleinhenz Joseph , Koerber James T. , Lafrance-Vanasse Julien , Leaver-Fay Andrew , Lee Jae Hyeon , Lee Edith , Lee Donald , Liang Wei-Ching , Lin Joshua Yao-Yu , Lisanza Sidney , Loukas Andreas , Ludwiczak Jan , Mahajan Sai Pooja , Mahmood Omar , Mohammadi-Peyhani Homa , Nerli Santrupti , Park Ji Won , Park Jaewoo , Ra Stephen , Robinson Sarah , Saremi Saeed , Seeger Franziska , Sinha Imee , Sokol Anna M. , Tagasovska Natasa , To Hao , Wagstaff Edward , Wang Amy , Watkins Andrew M. , Wilson Blair , Wu Shuang , Zadorozhny Karina , Marioni John , Regev Aviv , Wu Yan , Cho Kyunghyun , Bonneau Richard , Gligorijević Vladimir
Published: February 2025

Abstract

Therapeutic antibody design is a complex multi-property optimization problem that traditionally relies on expensive search through sequence space. Here, we introduce “Lab-in-the-loop,” a paradigm shift for antibody design that orchestrates generative machine learning models, multi-task property predictors, active learning ranking and selection, andin vitroexperimentation in a semiautonomous, iterative optimization loop. By automating the design of antibody variants, property prediction, ranking and selection of designs to assay in the lab, and ingestion ofin vitrodata, we enable a holistic, end-to-end approach to antibody optimization. We apply lab-in-the-loop to four clinically relevant antigen targets: EGFR, IL-6, HER2, and OSM. Over 1,800 unique antibody variants are designed and tested, derived from lead molecule candidates obtained via animal immunization and state-of-the-art immune repertoire mining techniques. Four lead candidate and four design crystal structures are solved to reveal mechanistic insights into the effects of mutations. We perform four rounds of iterative optimization and report 3–100×better binding variants for every target and ten candidate lead molecules, with the best binders in a therapeutically relevant 100 pM range.
Eucalyptus cover as the primary driver of native forest bird reductions: evidence from a stand-scale analysis in NW Iberia
Authors: García-Fernández Fernando , Vidal María , Regos Adrián , Domínguez Jesús
Published: February 2025

The rapid expansion of exotic eucalyptus plantations across the Iberian Peninsula, particularly in northwest Spain, where they now cover 30% of the region’s forested area, has profoundly transformed rural landscapes, raising serious concerns about its impact on native biodiversity. This study investigates the influence of structural and floristic attributes of eucalyptus plantations and native forests on forest bird communities, focusing on species abundance and occurrence at the stand level. We conducted point count surveys and vegetation assessments across 240 plots, applying Generalized Linear Models (GLMs) and multimodel inference (MMI) to identify key drivers of avian diversity. Vegetation structure and composition differed substantially between native forests and eucalyptus plantations. Bird species richness and abundance were significantly lower in eucalyptus plantations. The proportion of eucalyptus emerged as the strongest predictor of these reductions, likely due to the limited availability of key resources such as natural cavities and arthropods. Mature native trees were pivotal in supporting forest bird species, particularly those associated with mature forest ecosystems. In contrast, mature eucalyptus trees failed to serve as adequate surrogates for mature native trees, benefiting only a small subset of forest specialists. Similarly, the well-developed shrub layer in eucalyptus plantations provided limited support for generalist bird species. To mitigate biodiversity loss, we recommend integrating unmanaged retention strips within eucalyptus plantations to enhance habitat heterogeneity and structural diversity, ensuring critical resources for birds and other forest wildlife while balancing forestry productivity with conservation goals.
A gene-based model of fitness and its implications for genetic variation: Genetic and inbreeding loads
Authors: Johri Parul , Charlesworth Brian
Published: February 2025

In the companion paper to this, we examined the consequences for patterns of linkage disequilibrium of the “gene” model of fitness, which postulates that the effects of recessive or partially recessive deleterious mutations located at different sites within a gene fail to complement each other. Here, we examine the consequences of the gene model for the genetic and inbreeding loads, using both analytical and simulation methods, and contrast it with the frequently used “sites” model that allows allelic complementation. We show that the gene model results in a slightly lower genetic load, but a much smaller inbreeding load, than the sites model, implying that standard predictions of mutational contributions to inbreeding depression may be overestimates. Synergistic epistasis between pairs of mutations was also modeled, and shown to considerably reduce the inbreeding load for both the gene and sites models. The theoretical results are discussed in relation to data on inbreeding load inDrosophila melanogaster.
Phospholipid esters from herring roe promotes SPM biosynthesis in human monocyte-derived macrophages and a keratinocyte/fibroblast co-culture with implications for the treatment of psoriasis
Authors: Ringheim-Bakka Thomas A. , Saliani Amitis , Østbye Tone-Kari K. , Mildenberger Jennifer , Dooley Matthew , Busygina Maftuna , Pedersen Mona E. , Solberg Nina T. , Dalli Jesmond , Gammelsæter Runhild
Published: February 2025

Abstract

Immune-mediated inflammatory disease (IMID) is a major public health issue which can affect a number of organs and tissues with a profound impact on quality of life and often present with comorbidities. Psoriasis is a chronic IMID affecting the skin which presents with both local and systemic inflammation as part of its pathophysiology. An oil rich in polar lipids extracted from the roe sacks of herring has been shown to have immunomodulatory functions and to improve the clinical symptoms and impact inflammatory cytokine pathways in psoriasis in a clinical trial. The lipidic nature of herring roe oil and its high content of marine polyunsaturated fatty acids could suggest involvement of lipid mediator pathways for the observed alleviation of psoriatic inflammation. Of particular interest is the super-family of lipid mediators termed specialized pro-resolving mediators (SPMs), due to their known involvement in the resolution of inflammation and return to homeostasis. We have therefore explored the influence of herring roe oil and phospholipid esters from herring roe on lipid mediator and SPM biosynthesis in IFN-γ and LPS-stimulated human monocyte-derived macrophages and an IL-17A-stimulated skin cell co-culture with keratinocytes and fibroblasts. Lipid mediators including SPMs were quantified from resulting cell supernatants using a validated LC-MS/MS protocol. In these experiments we observed broad SPM biosynthesis with dominant upregulation of RvE2 and RvE3 in both cell systems and upregulation of DHA-derived SPMs such as RvD2 and PDX. Observations of PCTR2 in the macrophage cell supernatants also indicate activation of reparative pathways upon treatment with herring roe oil. In conclusion, we observed a promotion of SPM biosynthesis associated with a shift towards a protective and possibly reparative macrophage phenotype as well as promotion of biosynthesis of pro-resolving lipid mediators in a skin cell co-culture, thus demonstrating a possible mechanism for resolution of inflammation in the skin niche using herring roe oil.
Filament transport supports contractile steady states of actin networks
Authors: Sciortino Alfredo , Orhant-Prioux Magali , Guerin Christophe , Bonnemay Louise , Takagi Yasuharu , Sellers James , Colin Alexandra , Théry Manuel , Blanchoin Laurent
Published: February 2025

In all eukaryotic cells, the actin cytoskeleton is maintained in a dynamic steady-state. Actin filaments are continuously displaced from cell periphery, where they assemble, towards the cell’s center, where they disassemble. Despite this constant flow and turnover, cellular networks maintain their overall architecture constant. How such a flow of material can support dynamic yet steady cellular architectures remains an open question. To investigate the role of myosin-based forces in contractile steady-states of actin networks, we used a reconstitutedin vitrosystem based on a minimal set of purified proteins, namely actin, myosin and actin regulators. We found that, contrary to previous bulk experiments, when confined in microwells, the actin network could self-organize into ordered arrangements of contractile bundles, flowing continuously without collapsing. This was supported by three-dimensional fluxes of actin filaments, spatially separated yet balancing each other. Unexpectedly, maintaining these fluxes did not depend on filament nucleation or elongation, but solely on filament transport. Ablation of the contractile bundles abolished the flux balance and led to network collapse. These findings demonstrate that the dynamic steady state of actin networks can be sustained by filament displacement and recirculation, independently of filament assembly and disassembly.

Significance Statement

Cellular structures continuously self-renew, with new material constantly being added and removed while maintaining overall structural stability. This is particularly true for the actin cytoskeleton, whose components are continuously assembled, displaced, and reassembled. Understanding this process is fundamental to uncovering how cells regulate their architecture and adapt to stimuli.

Here, we reconstitute an in vitro actomyosin network capable of contracting steadily over time without collapsing, relying solely on myosin-based transport. These findings demonstrate that a minimal system consisting of actin and molecular motors can effectively recapitulate the ability of actin networks to self-organize into stable yet dynamic architectures.
Excavating Podocyte-Protective Targets of phloroglucinol-terpene hybrids Utilizing AI Models and Omics Analysis
Authors: Chen Ting , Liu Xiaoyan , Zhu Juan , Zhang Xinting , Zhang Jianhui , Yu Hongping , Xu Ziyan , Wang Dingyan , Zhu Yaobin , Zhong Feisheng , Luo Jiewei
Published: February 2025

Lupus nephritis (LN) is a multifactorial autoimmune inflammatory disorder, with podocyte dysfunction or structural abnormalities playing a pivotal role in its pathogenesis.Eucalyptusleaves, traditionally employed in folk medicine, have demonstrated notable efficacy in managing non-infectious inflammations. Eucarbwenstols D (R14) is a novel phloroglucinol-terpene that has been isolated fromEucalyptus robusta. To further refine potential targets, we utilized an AI scoring system and successfully identified the epidermal growth factor receptor (EGFR) as the novel target of R14. This discovery was built upon the foundation of transcriptome and connectivity mapping (CMap) analysis. Molecular docking and molecular dynamics simulations were employed to analyze the interaction between R14 and EGFR, surface plasmon resonance (SPR) and homogeneous time-resolved fluorescence (HTRF) assays were utilized to accurately quantify the binding affinity between R14 and EGFR. Western blot (WB) and immunofluorescence assays were then conducted to explore the downstream signaling pathways initiated by EGFR, specifically the PI3K/AKT/mTOR pathway. These assays demonstrated that R14 modulates the expression of apoptotic proteins Bax and Bcl-2 through this pathway, thereby exerting a protective effect on podocytes from undergoing apoptosis. The modulation of key podocyte proteins, nephrin and podocin, further substantiates this protective effect. Overall, we have applied a novel AI algorithm model that transcends bioinformatics analysis to precise identification of the novel podocyte target of R14. In this study, R14 was identified for the first time as a novel scaffold compound for EGFR inhibition. Moreover, R14 has demonstrated its capacity to inhibit podocyte apoptosis, thereby protecting these critical cells. This discovery establishes a robust theoretical foundation for the use of phloroglucinol-terpene hybrids (PTHs) in the treatment of LN.
Meltome Atlas ofArabidopsis thalianaProteome: A Melting Temperature-Based Identification of Heat & Cold Resistant Proteins
Authors: Mohanta Karan Martens , Mohanta Tapan Kumar
Published: February 2025

The study elucidated the thermal properties of the entireArabidopsis thalianaproteome by considering the melting temperature (Tm) and the melting temperature index (TI). In total, 48359 protein sequences were analyzed, and the melting temperature of the proteins was recorded in three groups (Tm < 55°C, 55-65°C, and > 65°C). The Tm index of theA. thalianaproteome ranged from -15.6008 (< 55°C) to 9.605 (> 65°C). At least 22826 proteins were found in the Tm group of 55°C to 65°C, 20640 proteins were found in the Tm group of > 65°C, and only 4893 proteins were found in the Tm group of < 55°C. The mediator of RNA polymerase II transcription subunit-like protein was found to possess the highest Tm index (9.60), while the NADH dehydrogenase 5B subunit was found to contain the lowest TI (-15.60). The amino acid composition analysis of theA. thalianaproteome revealed that the frequency of Ala, Asp, Glu, Gly, Lys, Gln, and Val increased with the increase in Tm, while the amino acids Cys, Phe, and Trp decreased with the increase in the Tm of theA. thalianaproteome. The molecular mass of theA. thalianaproteome ranged from 0.149 to 611.888 kDa, and protein in the Tm group at 55-65°C showed the highest average molecular mass. The machine learning analysis revealed an increase in the molecular mass positively correlated with the increase in the Tm of the proteins. The codon usage pattern revealed, the codon pair prefer the Tm group specific occurrence where ATG-ATG, CAA-CAA codon pairs were predominated. Relative synonymous codon usage of the three Tm groups revealed AGA (Arg) and CCA (Pro) were the preferred codons for the low and high Tm group DNA sequences, respectively. Codon context analysis revealed the presence of preferences of the Tm group specific codon pairing. There was a variation in the nucleotide position of the codons in different Tm groups. Evolutionary study revealed, gene duplication was the predominant evolutionary feature and all of the studied genes in the three Tm group undergone duplication. Codon context analysis revealed distinct clustering pattern in high Tm protein group. The study underscores the role of amino acid composition, molecular mass, and codon usage in determining the thermal stability of the proteins in theA. thaliana. The study reflected the evolution of high Tm-adapting genes through gene duplication, highlighting the role of gene and genome evolution towards encoding high Tm proteins for stress resilience.
Computational modeling of human genetic variants in mice
Authors: Dong Kexin , Gould Samuel I. , Li Minghang , Sánchez Rivera Francisco J.
Published: February 2025

Mouse models represent a powerful platform to study genes and variants associated with human diseases. While genome editing technologies have increased the rate and precision of model development, predicting and installing specific types of mutations in mice that mimic the native human genetic context is complicated. Computational tools can identify and align orthologous wild-type genetic sequences from different species; however, predictive modeling and engineering of equivalent mouse variants that mirror the nucleotide and/or polypeptide change effects of human variants remains challenging. Here, we present H2M (human-to-mouse), a computational pipeline to analyze human genetic variation data to systematically model and predict the functional consequences of equivalent mouse variants. We show that H2M can integrate mouse-to-human and paralog-to-paralog variant mapping analyses with precision genome editing pipelines to devise strategies tailored to model specific variants in mice. We leveraged these analyses to establish a database containing > 3 million human-mouse equivalent mutation pairs, as well asin silico-designed base and prime editing libraries to engineer 4,944 recurrent variant pairs. Using H2M, we also found that predicted pathogenicity and immunogenicity scores were highly correlated between human-mouse variant pairs, suggesting that variants with similar sequence change effects may also exhibit broad interspecies functional conservation. Overall, H2M fills a gap in the field by establishing a robust and versatile computational framework to identify and model homologous variants across species while providing key experimental resources to augment functional genetics and precision medicine applications. The H2M database (including software package and documentation) can be accessed athttps://human2mouse.com.
Interactive effect ofMoringa oleiferamediated green nanoparticles and arbuscular mycorrhizal fungi on growth, root system architecture, and nutrient uptake in maize (Zea maysL.)
Authors: Ain Qurat ul , Hussain Hafiz Athar , Rahman Lutfur , Zhang Qingwen , Rehman Asma , Hussain Saddam , Uddin Saleem , Imran Asma
Published: February 2025

The synergistic interaction between green nanoparticles (NPs) and mycorrhizal fungi promotes plant growth by improving nutrient absorption, optimizing root function, and stress resistance. In this study, we explored the impact of arbuscular mycorrhizal fungus (AMF)Funnaliformis mosseaeandMoringa oleiferamediated green NPs viz; iron oxide (FeO), zinc oxide (ZnO), and Zn doped FeO (Zn/Fe) NPs, both individually and in combination, on maize growth, root system architecture, organic acids production, mycorrhizal colonization, and nutrients uptake. Prior to NP synthesis, metabolomic analysis ofMoringa oleiferaleaves was conducted to characterize its bioactive compounds. The structural properties of green synthesized NPs confirmed by characterization using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, UV-Vis spectrophotometry, and X-ray diffraction (XRD). The results showed that all individual and combined treatments of AMF and green NPs significantly enhanced maize growth compared to the control. Among the single NP treatments, Zn/Fe NPs exhibited superior performance over FeO and ZnO. However, when combined with AMF, ZnO and Zn/Fe NPs induced the highest growth responses than FeO NPs. The ZnO NPs proved most compatibility with AMF for improving colonization in maize roots, whereas FeO and Zn/Fe NPs reduced colonization efficiency. Furthermore, combination of AMF and ZnO NPs (AMF+ ZnO) noted as most prominent treatment for improvement of maize growth compared to other all treatments, highlighting the potential of AMF+ ZnO NPs for sustainable agricultural applications.
The pulvinar regulates plasticity in human visual cortex
Authors: Acquafredda Miriam , Kurzawski Jan W. , Biagi Laura , Tosetti Michela , Morrone Maria Concetta , Binda Paola
Published: February 2025

In normally sighted human adults, two-hours of monocular deprivation is sufficient to transiently alter ocular dominance. Here we show that this is associated with a reduction of functional connectivity between the pulvinar and early visual cortex, selective for the pulvinar-to-V1 directionality. Our results support a revised model of adult V1 plasticity, where short-term reorganization is gated by modulatory signals relayed by the pulvinar.
Genome-wide profiling of tRNA modifications reveal the presence of divergent signatures inPlasmodium falciparum
Authors: Li Qian , Veith Ylva , Christ Elena , Ankarklev Johan , Larsson Ola , Chan Sherwin Chun-Leung
Published: February 2025

tRNAs are known to be extensively decorated with various nucleotide modifications, which can modulate the biological properties of tRNAs, such as promoting translation efficiency or fidelity, influencing codon preference and stabilizing tertiary structure of tRNAs. Dynamic alteration of the tRNA modifications, particularly under stress, are conserved gene regulatory mechanisms employed by cells across the kingdoms of life. The malaria-causingPlasmodium falciparum, which has a highly AT-biased genome, is reliant on a non-redundant set of tRNA genes to decode distinct and codon-skewed transcriptomes across its developmental stages. This genomic feature highlights the regulatory potential of tRNA modifications and warrants studies on how the tRNA epitranscriptome can impact gene regulatory function in this parasite. However, systematic studies of tRNA modifications inP. falciparumremain sporadic. In this study, we present a sequencing-based analysis of tRNA modifications inP. falciparumthrough optimizing the TGIRT-tRNA sequencing approach. The optimized protocol significantly reduces reverse transcription (RT) stop-induced short reads and enhances full-length cDNA synthesis, enabling the identification and stoichiometric estimation of a select nucleotide modifications at single-base resolution. We were able to identify seven types of conserved tRNA modifications and discovered two non-canonical signatures at A59 and U73 positions on specific nuclear-encoded tRNAs, which provides new insights into previously unreported modification sites. Our findings further reveal the dynamic nature of tRNA modifications during stage progression and under stress conditions.
PLXNB1 and other signaling drives a pathologic astrocyte state contributing to cognitive decline in Alzheimer’s Disease
Authors: Comandante-Lou Natacha , Lama Tsering , Chen Kevin , Zhang Jinglong , Hu Bin , Liu Shuhui , Heuer Sarah , Brennand Kristen J. , Schneider Julie , Barnes Lisa , Zhang Bin , Wang Minghui , Zou Hongyan , Friedel Roland H. , Ma Yiyi , Young-Pearse Tracy , Li Aiqun , Fujita Masashi , Bennett David , Zhang Ya , Menon Vilas , Klein Hans-Ulrich , Taga Mariko , De Jager Philip L.
Published: February 2025

Alzheimer’s disease (AD) is marked by the coordinated emergence of disease-associated cell states across multiple cell types. Here, we first performed a meta-analysis of single-nucleus transcriptomic (snRNAseq) data from 869 brains of diverse decedents, confirming the critical role of anSLC38A2highSMTNhighCACNA1Dhighastrocyte subset, Astrocyte 10 (Ast10), in AD and aging-related cognitive decline. We then investigated the signaling drivers of Ast10’s emergence in the aging brain, focusing on interactions among microglial and astrocytic subsets. Analysis of the snRNAseq data prioritized a set of ligands and receptors that are robustly predictive of Ast10 proportions across participants, and we confirm our predictions in multiple studies. Independent validation with spatial transcriptomics reveals striking colocalization of these prioritized ligands with the Ast10 signature in AD brain tissue, but not with other astrocytic states. Genetic ablation of a top receptorPLXNB1in murine and human iPSC-derived astrocytes decreased the Ast10 signature, confirming its regulatory role. Finally, we find that Ast10 may contribute to cognitive decline through synaptic loss and is associated with cognitive decline independent of AD. Thus, Ast10 and its regulators are potential points of convergence for multiple neurodegenerative mechanisms and may be promising targets for therapeutic development to preserve cognitive function.
Neurons exploit stochastic growth to rapidly and economically build dense radially oriented dendritic arbors
Authors: Ouyang Xiaoyi , Sutradhar Sabyasachi , Trottier Olivier , Shree Sonal , Yu Qiwei , Tu Yuhai , Howard Jonathon
Published: February 2025

Dendrites grow by stochastic branching, elongation, and retraction. A key question is whether such a mechanism is sufficient to form highly branched dendritic morphologies. Alternatively, are signals from other cells or is the topological hierarchy of the growing network necessary for dendrite geometry? To answer these questions, we developed a mean-field model in which branch dynamics is isotropic and homogenous (i.e., no extrinsic instruction) and depends only on the average lengths and densities of branches. Branching is modeled as density-dependent nucleation so there are no tree structures and no network topology. Despite its simplicity, the model predicted several key morphological properties of class IV Drosophila sensory dendrites, including the exponential distribution of branch lengths, the parabolic scaling between dendrite number and length densities, the tight spacing of the dendritic meshwork (which required minimal total branch length), and the radial orientation of branches. Stochastic growth also accelerated the overall expansion rate of the arbor. Therefore, stochastic dynamics is an economical and rapid space-filling mechanism for building dendritic arbors without external guidance or hierarchical branching mechanisms. Our model provides a general theoretical framework for understanding how macroscopic branching patterns emerge from microscopic dynamics.
Generative model for the first cell fate bifurcation in mammalian development
Authors: Avdeeva Maria , Chalifoux Madeleine , Joyce Bradley , Shvartsman Stanislav Y. , Posfai Eszter
Published: February 2025

The first cell fate bifurcation in mammalian development directs cells toward either the trophectoderm (TE) or inner cell mass (ICM) compartments in preimplantation embryos. This decision is regulated by the subcellular localization of a transcriptional co-activator YAP and takes place over several progressively asyn-chronous cleavage divisions. As a result of this asynchrony and variable arrangement of blastomeres, reconstructing the dynamics of the TE/ICM cell specification from fixed embryos is extremely challenging. To address this, we developed a live imaging approach and applied it to measure pairwise dynamics of nuclear YAP and its direct target genes, CDX2 and SOX2, key transcription factors of TE and ICM, respectively. Using these datasets, we constructed a generative model of the first cell fate bifurcation, which reveals the time-dependent statistics of the TE and ICM cell allocation. In addition to making testable predictions for the joint dynamics of the full YAP/CDX2/SOX2 motif, the model revealed the stochastic nature of the induction timing of the key cell fate determinants and identified the features of YAP dynamics that are necessary or sufficient for this induction. Notably, temporal heterogeneity was particularly prominent for SOX2 expression among ICM cells. As heterogeneities within the ICM have been linked to the initiation of the second cell fate decision in the embryo, understanding the origins of this variability is of key significance. The presented approach reveals the dynamics of the first cell fate choice and lays the groundwork for dissecting the next cell fate bifurcations in mouse development.
D-LMBmapX: Generalized Deep-Learning Pipeline for Automated Whole-brain Neural Circuitry Profiling Across Any Developmental Stages
Authors: Li Zhongyu , Li Peiqi , Pan Hangzhen , Adams Annabel M.J. , Huang Zuqi , Liu He , Li Jinjiang , Su Yaoyu , Zhong Baoming , Bray Liam , Sturgess Robyn N. , Zhu Jihua , Zhang Dingwen , Zhang Shaoting , Ren Jing
Published: February 2025

Understanding whole-brain circuitry development in mice has been hindered by the lack of tools for accurate and comprehensive analysis. No existing 3D brain atlas provides daily postnatal resolution, as constructing such atlases is highly labour-intensive. Axonal morphologies change dynamically, making reliable segmentation challenging, and many 2D datasets lack sufficient Z-resolution for cross-modality 3D analysis. Here, we present D-LMBmapX, a deep-learning pipeline for automated whole-brain circuitry profiling across postnatal development. D-LMBmapX constructs high-resolution 3D mouse brain atlases spanning seven postnatal stages and employs an adaptive registration strategy for whole-brain alignment at any postnatal day. It also integrates a foundation model for axon and soma segmentation, enabling the quantitative circuitry assessment across development. We implemented a diffusion model-based style transfer for cross-modality and cross-dimensional registration, validated by aligning genetically defined neuronal types from 2D ISH datasets to our 3D atlas. Using D-LMBmapX, we profiled whole-brain dopaminergic projections throughout postnatal maturation.
Sex-differences in catecholamine transporter expression in the rodent prefrontal cortex following repetitive mild traumatic brain injury and methylphenidate treatment
Authors: Papadopoulos Eleni , Abrimian Anna , Knapp Christopher P. , Loweth Jessica A. , Waterhouse Barry D. , Navarra Rachel L.
Published: February 2025

Irregular catecholamine transmitter activity is theorized to underly impaired prefrontal cortex (PFC)-mediated executive functions following repetitive mild traumatic brain injury (rmTBI). The psychostimulant, methylphenidate (MPH), enhances catecholamine neurotransmission by blocking reuptake transporters and is used off-label to treat post-TBI executive dysfunction. Although rmTBI and MPH have been shown to independently alter catecholamine transporter levels, the present report evaluated the interactive effects of rmTBI and a sub-chronic therapeutic dose of MPH on expression levels of vesicular monoamine transporter-2 (VMAT2) and norepinephrine reuptake transporter (NET) within subregions of the PFC in both male and female rats. Treatment with MPH restored rmTBI-induced reductions in transporter expression in females. However, in males subjected to rmTBI, MPH exacerbated reductions in transporter expression within the PFC. These results suggest MPH treatment produces beneficial effects in females but exaggerates pathological outcomes in males when used to treat post-rmTBI symptoms.
Removal of stripped protons produced in low-energy beam transport for superconducting linac
Authors: Liao Hui , Chen Weidong , Li Hui , Chen Benzheng , Xiao Yongchuan , Lv Yongjia , Cao Xiuxia , Liu Shengjin , Peng Jun , Feng Xinyuan , Liu Shunming
Published: February 2025

Superconducting linear accelerator (SCL) is commonly used to boost the negative hydrogen ion (H−) beam energy above the medium-β range. Stripped proton beam loss in SCL is one of the heat and radioactive source, which could threaten the operation of the SCL. This paper describes a novel technique for removing stripped protons produced in the low-energy beam transport section, the main area of H− beam stripping in the linac. The experiment is conducted at the China Spallation Neutron Source. The H− beam is bent by 1.8° before being focused into the radio-frequency quadrupole (RFQ) entrance. As a result of the differential pumping and optimized beam optics design, the bending magnet effectively removes over 99% of the stripped protons, resulting in a significant reduction of stripped protons captured by the RFQ and downstream linac.

Published by the American Physical Society
2025
Nonchiral
1T−TiSe2
creates circular dichroism in resonant x-ray diffraction via multipole scattering interference
Authors: Ueda Hiroki , Joly Yves , Staub Urs
Published: February 2025

Resonant x-ray diffraction (RXD) provides a unique capability to investigate electronically ordered states in matter. Importantly, circular dichroism in RXD can determine the absolute chirality formed by anisotropic multipole arrangement. Here, we demonstrate that the scattering interference between distinct atomic electric multipoles can create circular contrast in resonant RXD even in a nonchiral crystal. These general considerations are applied to 1T−TiSe2, where recently reported circular dichroism in RXD was used to claim a chiral charge density wave order. We show that the experimental observations are well reproduced by our calculations based on the centrosymmetric crystal structure. Our results not only illuminate a way for a better understanding of possible chiral electronic order but also propose a general approach to extract buried high-order atomic multipoles via circular contrast in RXD. Besides, we discuss the difference in the circular dichroism of RXD originated by crystal chirality in chiral crystals and the interference effect in nonchiral crystals.

Published by the American Physical Society
2025
Thin film flow over a spinning disk: Experiments and direct numerical simulations
Authors: Stafford Jason , Uzo Nwachukwu , Piccoli Enrico , Petit Camille , Matar Omar K.
Published: February 2025

The dynamics of thin liquid films flowing over a spinning disk is studied through a combination of experiments and direct numerical simulations. We consider a comprehensive range of interfacial flow regimes from waveless to three-dimensional (3D) waves, and for previously unexplored inertia-dominated conditions that have practical relevance. The transition between these regimes is categorized within a phase map based on two governing parameters that correspond to modified inverse Weber (λ) and Ekman numbers (rdisk). Our findings show that stationary two-dimensional (2D) spiral waves, which unfold in the direction of rotation from the Coriolis effect, transition to 3D waves with the emergence of small perturbations on the wavefronts. These nonstationary structures grow asymmetrically in the 2D-3D transitional region, and detach from the parent spiral wave to form wavelets or so-called Λ solitons. We show that during and after this wave formation process, flow circulations unique to the spinning disk arrangement are present within the main wave hump. Furthermore, when combined with observations of wall strain rates and topology within the film, these findings elucidate the mechanisms that underpin the apparent wave-induced interfacial turbulence effects observed for spinning disk flows.

Published by the American Physical Society
2025
Measurement resolution enhanced coherence for lattice fermions
Authors: Hurst Hilary M. , Teoh Yik Haw , Spielman I. B.
Published: February 2025

Weak measurement enables the extraction of targeted information from a quantum system while minimizing decoherence due to measurement backaction. However, in many-body quantum systems, backaction can have unexpected effects on wave-function collapse. We theoretically study a minimal many-particle model consisting of weakly measured noninteracting fermions in a one-dimensional lattice. Repeated measurement of the on-site occupation number with single-site resolution stochastically drives the system toward a Fock state, regardless of the initial state. This need not be the case for measurements that do not, even in principle, have single-site spatial resolution. We numerically show for systems with up to 16 sites that decreasing the spatial resolution strongly affects both the rate of stochastic evolution for each quantum trajectory and the allowed final states. The full Hilbert space can be partitioned into backaction-free subspaces (BFSs), the elements of which are indistinguishable for these measurements. Repeated measurements will drive any initial state into a single BFS, leading to a steady state that is a fixed point of the measurement process. We exactly calculate the properties of these BFSs for systems up to 32 sites, and we find that even for moderate reductions in measurement resolution, they yield nontrivial steady-state entanglement and coherence.

Published by the American Physical Society
2025