bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA origami directed integration of colloidal nanophotonic materials with silicon photonics
Authors: Luo Xin , Ranno Luigi , Sverko Tara , Lee Jae Young , Sbalbi Nicholas , Jones Annette , Chen Chi , Bawendi Moungi G. , Hu Juejun , Macfarlane Robert J. , Bathe Mark
Published: January 2025

Deterministic incorporation of colloidal quantum emitters into silicon-based photonic devices would enable major advances in quantum optics and nanophotonics. However, precisely positioning sub-10 nm particles onto micron-sized photonic structures with nanometer-scale accuracy remains an outstanding challenge. Here, we introduce Cavity-Shape Modulated Origami Placement (CSMOP) that leverages the shape programmability of DNA origami to selectively deposit colloidal nanomaterials within lithographically defined resist cavities patterned onto arbitrary photonic devices with high yield and orientation control. Soft-silicification-passivation stabilizes the deposited origami, while preserving their spatially programmable DNA hybridization sites, which enable site-specific attachment of plasmonic gold nanorods (AuNRs) and semiconductor quantum rods (QRs). This offers control over light scattering and emission polarization, respectively, with deterministic integration of individual QRs within silicon nitride waveguides, micro-ring resonators, and bullseye cavities. CSMOP thereby offers a general platform for the integration of colloidal nanomaterials into photonic circuits, with broad potential to empower quantum information science and technology.
Low-frequency ultrasound-mediated blood-brain barrier opening enables non-invasive lipid nanoparticle RNA delivery to glioblastoma
Authors: Elbaz Maya , Ad-El Nitay , Chulanova Yulia , Brier Dor , Goldsmith Meir , Bismuth Mike , Brosque Alina , Sher Divsha , Gutkin Anna , Bar-On Dana , Friedmann-Morvinski Dinorah , Peer Dan , Ilovitsh Tali
Published: January 2025

Ionizable Lipid Nanoparticles (LNPs) are an FDA-approved non-viral RNA delivery system, though their use for brain therapy is restricted by the blood-brain barrier (BBB). Focused ultrasound combined with microbubbles can disrupt the BBB, but delivering large particles requires balancing increased peak negative pressures while maintaining microvascular integrity. Herein, we optimized low-frequency ultrasound parameters to induce high-amplitude microbubble oscillations, enabling the safe delivery of LNPs across the BBB. First, BBB opening was assessed at different frequencies (850, 250, and 80 kHz) and pressures by monitoring the extravasation of Evans blue (~1 kDa). Next, the delivery of 4, 70, and 150 kDa Dextrans, LNPs entrapping Cy5-siRNAs (~70 nm in diameter), and LNPs entrapping mRNA (~100 nm in diameter) was evaluated via microscopy and bioluminescence. In a glioblastoma syngeneic mouse model, siRNA-Cy5-LNP was successfully delivered. A frequency of 850 kHz and 125 kPa pressure induced safe BBB opening, enabling delivery of both small molecules and LNPs. In healthy brains, LNP entrapping siRNAs delivery increased 10-fold compared to controls, and LNPs with mRNAs showed a 12-fold increase in bioluminescence after 24 hours. In glioblastoma tumors, LNPs with siRNAs delivery resulted in a 6.7-fold increase in fluorescence. This study paves the way for non-invasive LNP delivery to the brain, offering a versatile platform for brain therapies.
FlashFold: a standalone command-line tool for accelerated protein structure prediction
Authors: Saha Chayan Kumar , Roghanian Mohammad , Häussler Susanne , Guy Lionel
Published: January 2025

FlashFold is a fast, user-friendly tool for predicting protein structures and complexes. It can be installed locally on Linux or Mac operating systems, alleviating the computational needs, and eliminating reliance on third-party servers. FlashFold relies on a highly compact and adaptable built-in database to speed up the homology searching. Overall structure predictions are up to 3-fold faster than AlphaFold3 with sacrificing little or no accuracy. FlashFold is available athttps://github.com/chayan7/flashfold.
SOX9 plays an essential role in myofibroblast driven hepatic granuloma integrity and parenchymal repair during schistosomiasis-induced liver damage
Authors: Su Kim , Jokl Elliot , Costain Alice , Simpson Kara , Cheeseman Antonn , Phythian-Adams Alexander , Couper Kevin N , MacDonald Andrew S. , Piper Hanley Karen
Published: January 2025

Schistosomiasis is a neglected, and potentially lethal, parasitic disease that affects hundreds of millions of people worldwide. As part of the schistosome lifecycle, parasite eggs accumulate within the liver where they evoke intense granulomatous pathology, typified by a dense extracellular matrix (ECM) barrier, which serves to contain toxic egg secretions. In severe cases, this progressive and irreversible egg-evoked ECM deposition can lead to pathological scarring, impaired liver function and lethality. Thus, identifying the core regulators that govern ECM deposition may aid discovery of new therapeutic targets for schistosomiasis. The transcription factor Sex determining region Y-box 9 (Sox9) is a known regulator of pathological scaring. We found that, followingSchistosoma mansoniinfection, SOX9 was ectopically expressed in myofibroblasts within the granuloma and in surrounding hepatocytes. In the absence of SOX9, granuloma size was significantly diminished, and mice failed to produce a robust ECM barrier around eggs, resulting in more diffuse liver injury and scattered distribution of immune cells. Immunologically, SOX9 loss in both naïve and infected mice led to an increase in hepatic neutrophil and monocyte proportions, with the expansion of Ly6clomonocyte populations in infected SOX9 deficient mice only. Infected SOX9–deficient mice also displayed exaggerated Type 2 inflammation, including pronounced eosinophilia. These data highlight the importance of SOX9 for intact hepatic granuloma formation during schistosomiasis and suggest SOX9 or its related factors may provide attractive future targets for meeting the clinical need to limit and/or reverse fibrotic disease.

Author Summary

Mammalian infection with schistosome worms results in the deposition of parasite eggs in the liver, where they secrete organ damaging toxins. In response, the liver generates a cellular granuloma barrier rich in extracellular matrix to limit these secretions and protect the overall organ. As in other liver injuries, SOX9 becomes progressively expressed in multiple cell types during the time course of schistosome infection. To understand the role of SOX9 in the liver response to schistosomes we utilised a global SOX9 deficient mouse model. These mice show reduced and disorganised granuloma formation during schistosome infection, with disrupted hepatic immune profiles. This suggests that SOX9 is required to form a robust and coordinated granuloma barrier that limits liver damage in this important but neglected parasitic disease.
Strain background interacts with chromosome 7 aneuploidy to determine commensal and virulence phenotypes inCandida albicans
Authors: Mishra Abhishek , Solis Norma V. , Dietz Siobhan M. , Crouch Audra L. , Filler Scott G. , Anderson Matthew Z.
Published: January 2025

The human fungal pathobiontCandida albicansdisplays extensive genomic plasticity, including large-scale chromosomal changes such as aneuploidy. Chromosome trisomy appears frequently in natural and laboratory strains ofC. albicans. Trisomy of specific chromosomes has been linked to large phenotypic effects, such as increased murine gut colonization bystrainstrisomic for chromosome 7 (Chr7). However, studies of whole-chromosome aneuploidy are generally limited to the SC5314 genome reference strain, making it unclear whether the imparted phenotypes are conserved acrossC. albicansgenetic backgrounds. Here, we report the presence of a Chr7 trisomy in the “commensal-like” oral candidiasis strain, 529L, and dissect the contribution of Chr7 trisomy to colonization and virulence in 529L and SC5314. These experiments show that strain background and homolog identity (i.e., AAB vs ABB) interact with Chr7 trisomy to alter commensal and virulence phenotypes in multiple host niches.In vitrofilamentation was the only phenotype altered by Chr7 trisomy in similar ways across the two strain backgrounds. Oral colonization of mice was increased by the presence of a Chr7 trisomy in 529L but not SC5314; conversely, virulence during systemic infection was reduced by Chr7 trisomy in SC5314 but not 529L. Strikingly, the AAB Chr7 trisomy in the SC5314 background rendered this strain avirulent in murine systemic infection. Increased dosage ofNRG1failed to reproduce most of the Chr7 trisomy phenotypes. Our results demonstrate that aneuploidy interacts with background genetic variation to produce complex phenotypic patterns that deviate from our current understanding in the genome reference strain.

AUTHOR SUMMARY

Candida albicansis a clinically important fungus of humans that is also part of the microbiota that typically colonizes our bodies. Changes in the number of copies of chromosome 7 (Chr7) in the genome of the reference strain ofC. albicansenhances host colonization. We identified a third copy of Chr7 in a strain classified as a good colonizer of humans that doesn’t cause disease, mimicking the increased colonization of the reference strain. Here, we demonstrate that the number of copies of Chr7 alters phenotypes differently between these strains, and three copies of Chr7 does not universally produce a strain that is only a better commensal strain. Additionally, which copy of Chr7 in this diploid species exists as the third copy influences commensal and pathogen phenotypes. Therefore, trisomic changes of the same chromosome in differentC. albicansstrains have substantially different effects.
MutBERT: Probabilistic Genome Representation Improves Genomics Foundation Models
Authors: Long Weicai , Su Houcheng , Xiong Jiaqi , Zhang Yanlin
Published: January 2025

Motivation

Understanding the genomic foundation of human diversity and disease requires models that effectively capture sequence variation, such as single nucleotide polymorphisms (SNPs). While recent genomic foundation models have scaled to larger datasets and multi-species inputs, they often fail to account for the sparsity and redundancy inherent in human population data, such as those in the 1000 Genomes Project. SNPs are rare in humans, and current masked language models (MLMs) trained directly on whole-genome sequences may struggle to efficiently learn these variations. Additionally, training on the entire dataset without prioritizing regions of genetic variation results in inefficiencies and negligible gains in performance.

Results

We present MutBERT, a probabilistic genome-based masked language model that efficiently utilizes SNP information from population-scale genomic data. By representing the entire genome as a probabilistic distribution over observed allele frequencies, MutBERT focuses on informative genomic variations while maintaining computational efficiency. We evaluated MutBERT against DNABERT-2, various versions of Nucleotide Transformer, and modified versions of MutBERT across multiple downstream prediction tasks. MutBERT consistently ranked as one of the top-performing models, demonstrating that this novel representation strategy enables better utilization of biobank-scale genomic data in building pretrained genomic foundation models.

Availability

https://github.com/ai4nucleome/mutBERT

Contact

yanlinzhang@hkust-gz.edu.cn
Transcriptional Dynamics and Chromatin Accessibility in the Regulation of Shade-Responsive Genes in Arabidopsis
Authors: Paulisic Sandi , Boccaccini Alessandra , Dreos René , Ambrosini Giovanna , Guex Nicolas , Benstei Ruben Maximilian , Schmid Markus , Fankhauser Christian
Published: January 2025

Open chromatin regions host DNA regulatory motifs that are accessible to transcription factors and the transcriptional machinery. In Arabidopsis, responses to light are heavily regulated at the transcriptional level. Shade, for example, can limit photosynthesis and is rapidly perceived by phytochromes as a reduction of red to far-red light ratio (LRFR). Under shade, phytochromes become inactive, enabling PHYTOCHROME INTERACTING FACTORs (PIFs), particularly PIF7, to promote genome-wide reprogramming essential for LRFR responses. An initial strong and fast regulation of shade-responsive genes is followed by attenuation of this response under prolonged shade. We wanted to determine whether the transcriptional response to shade depends on chromatin accessibility. For this, we used ATAC-seq to profile the chromatin of seedlings exposed to short (1h) and long (25h) simulated shade. We found that PIF7 binding sites were accessible for most early target genes before LRFR treatment. The transcription pattern of most acute shade-responsive genes correlated with a rapid increase in PIF levels and chromatin association at 1h, and its decrease at 25h of shade exposure. For a small subset of acutely responding genes, PIFs also modulate chromatin accessibility at their binding sites early and/or late in the response to shade. Our results suggest that in seedlings a state of open chromatin conformation allows PIFs to easily access and recognize their binding motifs, rapidly initiating gene expression triggered by shade. This transcriptional response primarily depends on a transient increase in PIF stability and gene occupancy, accompanied by changes in chromatin accessibility in a minority of genes.
Clinical and Genetic Determinants of Glioblastoma Multiforme Survival: A Retrospective Analysis
Authors: Gutiérrez-Arroyo Julia L. , Gallego-Porcar Pia , Carbonell-Martinez Elvira , González-Bonet Luis G. , Ibañez Maria Victoria , Díaz-Ruiz María , Caballero-Arzapalo Hugo , Soto Ariadna , Garcia-Oriola Guillermo , Borras-Moreno Jose Maria , Martinez-Cadenas Conrado , Marques-Torrejon Maria Angeles
Published: January 2025

Glioblastoma, the most aggressive primary brain tumour in adults, has a poor prognosis and limited survival despite advances in treatment. This study analysed 61 patients with glioblastoma multiforme treated at the General University Hospital of Castellon, Spain, focusing on clinical, tumour-specific and genetic factors influencing disease outcome. Variables included age, sex, BMI, extent of surgical resection, and use of radiotherapy or chemotherapy. Tumour characteristics assessed included location, size, proximity to the ventricular system and surgical approach. Genetic mutations in theIDH, EGFR, TP53andCDKN2Agenes were also analysed. Kaplan-Meier analysis was used to assess the impact of these factors on overall survival and progression-free survival. A significant finding was the strong association between surgical approach, tumour proximity to the ventricular system and survival: patients with tumours closer to the ventricles had significantly shorter survival, highlighting the critical role of spatial tumour characteristics in glioblastoma multiforme outcomes. These results suggest that integrating clinical, genetic and spatial tumour data into personalised treatment approaches could improve prognosis. Understanding these factors is critical to developing more effective strategies to meet the challenges of this aggressive and complex disease.
A rapidly closing window for coral persistence under global warming
Authors: Bozec Yves-Marie , Adam Arne A.S. , Nava Beatriz Arellano , Cresswell Anna K. , Haller-Bull Vanessa , Iwanaga Takuya , Lachs Liam , Matthews Samuel A. , McWhorter Jennifer K. , Anthony Kenneth R.N. , Condie Scott A. , Halloran Paul R. , Ortiz Juan-Carlos , Riginos Cynthia , Mumby Peter J.
Published: January 2025

Summary paragraph

Coral reefs around the world are threatened by recurrent marine heatwaves causing mass coral bleaching and mortality1. Mitigating future warming impacts requires strategic management2that adopts a long-term lens. Global analyses of projected heatwaves3,4are critical for decision-making but how disturbance refugia, coral life-histories and adaptation interact with warming is unknown. Here, we simulate coral eco-evolutionary dynamics across >3,800 individual reefs of Australia’s iconic Great Barrier Reef under the current suite of climate projections5. We forecast a rapid coral decline before mid-century regardless of emissions scenario. Under the most likely warming6, corals may continue to decline throughout the century. However, corals may recover after mid-century provided that warming is sufficiently slow, allowing thermal adaptation to keep pace with temperature changes – as projected if warming does not exceed 2°C. Higher emission scenarios would drive most reefs to a near collapse. Future resilient reefs were mostly found in bleaching refugia, which also possessed a greater diversity of thermal phenotypes. Although cool-adapted corals disperse to thermal hotspots, there was no evidence of ‘gene swamping’ undermining thermal adaptation. While opportunities exist to build management strategies that promote adaptation in thermal refugia and warm spots, curbing the rate of warming by 2050 is crucial for coral persistence.
Invaders' trophic position and their direct and indirect relationship influence on resident food webs
Authors: Moreh Agnes , Scheuring Istvan
Published: January 2025

Many ecosystems are undergoing simultaneous colonization and spread of multiple alien species. Invaders often negatively affect communities by reducing population sizes of resident species or even decreasing community diversity through extinctions. Direct and indirect interactions between them can amplify or mitigate their impacts on native communities. In this study, we compare the effects of two invaders on the resident model food webs under two scenarios: separate versus simultaneous invasion. We examined the resident food webs' response from two perspectives: the number of extinct species as a measure of diversity loss, and the net change in total biomass of the food web. Using dynamic simulations based on the Allometric Bioenergetic Model, we tracked these changes in silico and compared the results of the two scenarios. We examined how the invaders' trophic positions relative to each other and their direct/indirect interactions influence the additive or non-additive nature of the outcomes of their co-invasion. Our results have corroborated previous field and experimental observations, showing that when co-occurring invaders occupy different trophic levels, their combined effects may be dampened if one invader preys on the other. Further, we have shown that the probability of synergistic effect increases when invaders form a trophic cascade or share a common predator. However, we have also shown that all of these relationships are influenced by i) the metric used to track changes in the resident community, ii) the trophic level at which the invasion occurs, and iii) whether the invader has a predator (either resident or another invader).
Time-dependent chromatin maturation during 3D spheroid culture improves preclinical modeling of non-small cell lung cancer
Authors: Darracq Anaïs , Sgarioto Nicolas , Huot Marielle , McInnes Gabrielle , Meant Antoine , Langford Alexandra , Villarreal Oscar D , Marois François , Caron Maxime , Saint-Onge Pascal , Leclerc Severine , Cagnone Gaël , Andelfinger Gregor , Richard Stéphane , Sinnett Daniel , McGraw Serge , Raynal Noël J-M
Published: January 2025

Non-small cell lung cancer (NSCLC) is the deadliest cancer worldwide. Therapeutic progress stagnate, highlighting the complexity to replicate NSCLC in preclinical models. Drug discovery studies rely mostly on cancer cells in two-dimension (2D), which poorly predict drug efficacy in patients. There is a growing interest in three-dimensional (3D) preclinical models, such as 3D spheroids, to better model tumor phenotype and improve therapeutic prediction. However, a comprehensive view of 3D culture methods impact on transcriptomes, epigenomes and pharmacological responses and their correlations to NSCLC tumors is still missing. Here, we demonstrate that NSCLC spheroids undergo time-dependent transcriptomic and epigenomic changes, which peak after 3 weeks of culture. While DNA methylome remained stable, chromatin methylation and acetylation marks gained features of advanced NSCLC in a time-dependent manner. Single-cell transcriptomic profiling of spheroids demonstrated that time of 3D culture improved the correlation to NSCLC tumors. Moreover, long-term culture of 3D spheroids increased drug screening predictability, by showing resistance to drugs that failed in NSCLC patients (such as HDAC inhibitors) while demonstrating novel pharmacological vulnerabilities and synergistic interactions (such as combination of PRMT and HDAC inhibitors). Strikingly, reverting 3D spheroids back to 2D culture rapidly reversed transcriptomic, epigenetic and pharmacological signatures acquired after 3 weeks of 3D culture, highlighting the critical impact of cell culture conditions on NSCLC phenotype. Collectively, our findings demonstrate that implementing a time-dependent maturation process into 3D spheroid culture induces chromatin and transcriptomic changes that enhance NSCLC preclinical modeling.
A Diverse Genetic Basis for Metabolic Reactions is Revealed Through Pangenome analysis
Authors: Ardalani Omid , Phaneuf Patrick V. , Krishnan Jayanth , Li Gaoyuan , Burrows Joshua , Nielsen Lars K. , Palsson Bernhard O.
Published: January 2025

Sequenced genomes for thousands of strains of a bacterial species allow for a comprehensive analysis of its pangenome. We present a pangenome study ofEscherichia coli’s metabolism by formulating ‘gene-to-protein-to-reaction associations’ (GPRs) for about 2,700 metabolic reactions in 2,377 fully sequenced strains. On one hand, these GPRs reconstruct strain–specific networks that allow computational predictions (and experimental validation) of metabolic phenotypes, while on the other hand, they give the genetic basis for a given metabolic reaction in every strain. A pangenome-wide analysis of GPRs shows that: 1) We can reveal the genetic basis for a specific metabolic property at the species level; 2) The genetic basis for many metabolic reactions is diverse; 3) Many rare genes show variation in the gene’s genomic neighborhood which often contain genes from transposable elements, 4) Many rare genes show large-scale fragmentation and horizontal gene transfer (>11,000 rare genes in 2,377 strains); and 5) The aromatic amino acids and branched chain amino acids pathways are enriched with rare genes, with Acetolactate synthase having 29 distinct genes. Thus, analysis of GPRs across the pangenome reveals a complex dynamic evolutionary history of metabolism, revealing the role of conserved, fragmented, and horizontally transferred metabolic genes.
End-to-end Learning of Safe Stimulation Parameters for Cortical Neuroprosthetic Vision
Authors: Küçükoğlu Burcu , Rueckauer Bodo , de Ruyter van Steveninck Jaap , van der Grinten Maureen , Güçlütürk Yağmur , Roelfsema Pieter R. , Güçlü Umut , van Gerven Marcel
Published: January 2025

Direct electrical stimulation of the brain via cortical visual neuroprostheses is a promising approach to restore basic sight for the visually impaired by inducing a percept of localized light called ‘phosphenes’. Apart from the challenge of condensing complex sensory information into meaningful stimulation patterns at low temporal and spatial resolution, providing safe stimulation levels to the brain is crucial. We propose an end-to-end framework to learn optimal stimulation parameters (amplitude, pulse width and frequency) within safe biological constraints. The learned stimulation parameters are passed to a biologically plausible phosphene simulator which takes into account the size, brightness, and temporal dynamics of perceived phosphenes. Our experiments on naturalistic navigation videos demonstrate that constraining stimulation parameters to safe levels not only maintains task performance in image reconstruction from phosphenes but consistently results in more meaningful phosphene vision, while providing insights into the optimal range of stimulation parameters. Our study presents a stimulus-generating encoder that learns stimulation parameters (1) satisfying safety constraints, and (2) maximizing the combined objective of image reconstruction and phosphene interpretability with a highly realistic phosphene simulator accounting for temporal dynamics of stimulation. End-to-end learning of stimulation parameters this way enables enforcement of critical biological safety constraints as well as technical limits of the hardware at hand.
A non-invasive approach to awake mouse fMRI compatible with multi-modal techniques
Authors: Laxer Sam , Eed Amr , Bellyou Miranda , Zeman Peter , Gilbert Kyle M , Naderi Mohammad , Menon Ravi S
Published: January 2025

Abstract

Mouse functional magnetic resonance imaging (fMRI) studies contribute significantly to neuroimaging research, playing an important role in advancing our understanding of the human brain. Efforts to scan mice in the awake state and avoid the use of anesthesia have demonstrated many benefits. However, the majority of current awake fMRI approaches involve head fixation through invasive surgical means. These approaches are limited for several reasons including increased subject morbidity and mortality, prolonged study timelines due to surgical recovery, a higher risk of susceptibility artifacts contaminating T2*-weighted images and obstructed access to the head for multi-modal recording techniques such as electrophysiology and fibre photometry. To address this need, we propose a non-invasive restraint to scan mice in the awake state. The restraint was designed to be compatible with brain stimulation and recording approaches. It was evaluated on the basis of motion, fMRI data quality, and animal stress levels, and subsequently compared to a conventional headpost restraint. We found the proposed approach was effective at restraining mice across a broad range of weights without the need for any anesthesia for setup. Conservatively, acquiring 25% more data with the non-invasive restraint compensates for censored frames in high motion runs and results in comparable network spatial specificity to less motion-vulnerable headpost approaches. This validation of network robustness paired with its non-invasive nature makes it a favourable approach for applications requiring high-throughput and/or multimodal imaging studies.
Feature-Driven Whole-Tissue Imaging with Subcellular Resolution
Authors: Lin Jinlong , Marin Zach , Wang Xiaoding , Borges Hazel M. , N'Guetta Pierre-Emmanuel Y. , Luo Xuemei , Porter Baylee A. , Xue Yuanyuan , Islam Md Torikul , Ngo Tai , Aurora Arin B. , Zhao Hu , Conzen Suzanne D. , Morrison Sean J. , Liang Shuang , Zhong Zhenyu , O'Brien Lori L. , Dean Kevin M.
Published: January 2025

Understanding how subcellular structures and events shape tissue-wide phenomena remains a central challenge in biology. We present Multiscale Cleared Tissue Axially Swept Light-Sheet Microscopy (MCT-ASLM), a platform combining cm-scale imaging with targeted high-resolution interrogation of intact tissues in human-guided or autonomous modes. Capable of capturing fields of view up to 21 mm at micron-scale resolution, MCT-ASLM can seamlessly transition to submicron (~300 nm) isotropic resolution for targeted imaging. This versatility enables comprehensive studies of hierarchical organization and spatially complex processes, including mapping neuronal circuits in rat brains, visualizing glomerular innervation in mouse kidneys, and examining metastatic tumor microenvironments. By bridging subcellular to tissue-level scales, MCT-ASLM offers a powerful method for unraveling how local events contribute to global biological phenomena.
Wearable Photonic Device for Multiple Biomarker Sampling and Detection Without Blood Draws
Authors: Lin Zuan-Tao , Jana Biswabandhu , Korupolu Sandeep , Kong Yifei , Liu Guishi , Dong Yan , Li Yongli , Zhang Quanwei , Shou Wan , Upadhyay Prabhat , Wu Mei X.
Published: January 2025

Blood draws or phlebotomy using needles have been practiced in clinics for several centuries and it often causes pain, discomfort, and inconvenience. Herein, we create a wearable photonic device by integrating a microlens array (MLA) and an optic microneedle array (OMNA) functionalized with immunobinding capacity for safe and needle-free biomarker sampling and detection. The MLA-integrated OMNA amplified and transmitted LED light at 595 nm into the skin through the OMNA, bypassing the light-absorbing melanin in the epidermal layer, and evenly distributing it in the capillary-enriched dermis. The 595 nm light was preferably absorbed by hemoglobin (Hb) and oxygen-Hb within the capillaries, triggering thermal dilation of capillaries without damaging them or causing petechiae. The light illumination resulted in remarkable increases in the concentrations of various blood biomarkers in the skin owing to capillary dilation and biomarker extravasation. These extravasated biomarkers bound specifically to the OMNA, which was covalently decorated with capture antibodies, each microneedle immobilized with one specific antibody. The multi-functional OMNA was extensively modified to amplify the immunobinding signals and achieve sensitivity superior to that of enzyme-linked immunosorbent assay (ELISA) kits. As a proof of concept, we validated the functionality of the prototype for minimally invasive sampling and precise multiplexed blood biomarker detection in two mouse models to quantify acute inflammation and specific antibody production. This cost-efficient device provides a promising platform for blood-free, multiplexed detection of blood biomarkers.
BioMaster: Multi-agent System for Automated Bioinformatics Analysis Workflow
Authors: Su Houcheng , Long Weicai , Zhang Yanlin
Published: January 2025

Motivation

The rapid expansion of biological data has significantly increased the complexity of bioinformatics workflows, which often involve intricate, multi-step processes. These tasks demand considerable manual effort from bioinformaticians, creating inefficiencies and limiting scalability. Recent advancements in large language model (LLM)-powered agents offer promising solutions to streamline and automate these workflows. However, existing automated systems, while effective for short, well-defined tasks, often struggle with long, multi-step workflows due to challenges such as error propagation, limited adaptability to emerging tools, and the inability of LLMs to generalize to niche bioinformatics tasks. Achieving effective workflow automation requires robust task coordination, dynamic knowledge retrieval, and mechanisms to ensure errors are identified and resolved before they impact downstream processes.

Results

We present BioMaster, a multi-agent framework designed to automate and streamline complex bioinformatics workflows. BioMaster incorporates specialized agents with role-based responsibilities, enabling precise task decomposition, execution, and validation. It leverages Retrieval-Augmented Generation (RAG) to dynamically retrieve domain-specific knowledge, improving adaptability to new tools and niche analyses. BioMaster also introduces enhanced control over input and output validation to ensure pipeline consistency and employs a memory management strategy optimized for handling long workflows. Experiments across diverse bioinformatics tasks, including RNA-seq, ChIP-seq, single-cell analysis, and Hi-C processing, demonstrate that BioMaster significantly outperforms existing methods in accuracy, efficiency, and scalability. By addressing key limitations in workflow automation, BioMaster offers a robust solution for modern bioinformatics challenges.

Availability

https://github.com/ai4nucleome/BioMaster

Contact

yanlinzhang@hkust-gz.edu.cn
Achievement-Based Differences in Cognitive-Emotional Interplay During Classroom Learning: A Multimodal Analysis with Experience Sampling Method
Authors: Liu Xiaobo , Fu Lan , Yang Zihao , Zhang Zheng , Zhang Yu
Published: January 2025

Background

The relationship between cognition and emotion during learning is crucial for educational theories and has been under debate for a long time, from the ancient philosophy to current scientific analyses. However, the relationship may not be uniform and may vary across diverse individual groups.

Aims

Therefore, this study aims to explore whether the relationship between cognition and emotion varies across different student groups. Furthermore, it examines whether neurophysiological evidence can provide insights into such group differences.

Sample

The study involved 22 high school students (11 high-performing and 11 low-performing) over 13 math lessons. Surveys were administered three times during each lesson, yielding a multilevel dataset with 777 samples.

Methods

The experience sampling method was employed to gather data on cognitive and emotional states periodically, as well as their regulations. Simultaneously, multimodal neurophysiological data, including electroencephalograph (EEG), electrodermal activity (EDA), and photoplethysmography (PPG), were collected during classroom learning to analyze the relationship further.

Results

Cognitive state, cognitive regulation, emotional state, and emotional regulation were highly correlated overall. In high-performing students, the association was higher than that in low-performing students, especially at the level of within-subject repeated-measures. Multimodal data revealed the common neurophysiological basis of the correlated variation between cognition and emotion, and highlighted different neurophysiological patterns between high and low achievers.

Conclusions

The joint evidence from the experience sampling survey and neurophysiological measures reveals that the cognitive-emotional relationship differs by academic achievement levels, with high achievers revealing a more consistent variation between cognition and emotion. Such co-variation shares a common neurophysiological pattern with features associated with high student-teacher interaction and high concentration, further explaining the group differences.
Assessing predictive accuracy of species abundance models in dynamic systems
Authors: Brown Christopher J. , Buelow Christina , Stuart-Smith Rick D. , Barrett Neville , Edgar Graham , Oh Elizabeth
Published: January 2025

Cascading human pressures and environmental change are affecting the natural dynamics of animal populations. Forecasting population abundances from time-series data provides an important avenue for testing competing ecological theories, and for supporting conservation planning and sustainable use, yet changing system dynamics may lead to erroneous predictions. Predictions from a model fitted and tested on historical system dynamics may become irrelevant if system dynamics change. Here we describe methods to test forecast skill in a rapidly changing system where model parameters are likely to be non-stationary. We presented two ways to split time-series into training and test datasets so that training data were: 1) contemporary to the testing data (‘modern split’), and 2) not contemporary to the testing data (‘legacy split’). As a case-study, we use animal abundance data from a 30-year time-series from a global warming hotspot. We tested our approach on four temperate reef species with different temporal trends. The case-study and simulation tests confirmed larger forecast errors in legacy split when compared to the modern split. We found that the legacy split had errors that could be more than for times larger for a species that had a rapid collapse in abundance and non-stationary population dynamics. As expected for the species with rapid collapse, the legacy split estimated much higher forecast error than the modern split. Our approach is applicable to a large range of species and systems, including fisheries and threatened species population monitoring, where rapidly changing environments present threats to both the species and management efficacy. Accumulated lessons from across species and systems should shed light on critical generalities that precede broader ecosystem change.
Neural Changes to Transcranial Alternating Current Stimulation in the Gamma Range Over the Left Frontoparietal Network: A Preliminary eLORETA EEG Study
Authors: Lee Tien-Wen , Tramontano Gerald
Published: January 2025

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions can improve cognitive dysfunctions. This study aimed to explore the neural changes following transcranial electrical stimulation treatment. Electroencephalography (EEG) recordings were obtained from a cohort of 34 participants with various cognitive impairments before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were administered to the electrode positions F3 and P3 for 20 minutes of each session, following the 10-20 EEG convention. Using eLORETA, scalp-recorded signals were reconstructed into cortical current source density (CSD). We then assessed the differences in power and connectivity strength across multiple spectra (delta to gamma). We observed a consistent trend of decreased CSD at the stimulating sites across different spectra, most prominent at beta and gamma bands (P< 0.01). On the contrary, the right hemisphere showed a trend of increased CSD, which was likely mediated by inter-hemispheric rivalry. In addition, the connectivity strength between the left frontal and parietal regions increased significantly (P= 0.017). Artificial injections of tACS would de-synchronize regional oscillation and enhance inter-regional crosstalk. The pattern of neural changes was concordant with our previous tACS reports (5-Hz), suggesting common neural mechanisms driving the neurophysiological effects of tACS.
Genome-scale spatial mapping of the Hodgkin lymphoma microenvironment identifies tumor cell survival factors
Authors: Shanmugam Vignesh , Tokcan Neriman , Chafamo Daniel , Sullivan Sean , Borji Mehdi , Martin Haley , Newton Gail , Nadaf Naeem , Hanbury Saoirse , Barrera Irving , Cable Dylan , Weir Jackson , Ashenberg Orr , Pinkus Geraldine , Rodig Scott , Uhler Caroline , Macosko Evan , Shipp Margaret , Louissaint Abner , Chen Fei , Golub Todd
Published: January 2025

A key challenge in cancer research is to identify the secreted factors that contribute to tumor cell survival. Nowhere is this more evident than in Hodgkin lymphoma, where malignant Hodgkin Reed Sternberg (HRS) cells comprise only 1-5% of the tumor mass, the remainder being infiltrating immune cells that presumably are required for the survival of the HRS cells. Until now, there has been no way to characterize the complex Hodgkin lymphoma tumor microenvironment at genome scale. Here, we performed genome-wide transcriptional profiling with spatial and single-cell resolution. We show that the neighborhood surrounding HRS cells forms a distinct niche involving 31 immune and stromal cell types and is enriched in CD4+ T cells, myeloid and follicular dendritic cells, while being depleted of plasma cells. Moreover, we used machine learning to nominate ligand-receptor pairs enriched in the HRS cell niche. Specifically, we identified IL13 as a candidate survival factor. In support of this hypothesis, recombinant IL13 augmented the proliferation of HRS cellsin vitro. In addition, genome-wide CRISPR/Cas9 loss-of-function studies across more than 1,000 human cancer cell lines showed that IL4R and IL13RA1, the heterodimeric partners that constitute the IL13 receptor, were uniquely required for the survival of HRS cells. Moreover, monoclonal antibodies targeting either IL4R or IL13R phenocopied the genetic loss of function studies. IL13-targeting antibodies are already FDA-approved for atopic dermatitis, suggesting that clinical trials testing such agents should be explored in patients with Hodgkin lymphoma.
Endogenous retrovirus-drivenPcgf5plays critical roles in zygotic genome activation and noncanonical imprinting
Authors: Mashiko Satoshi , Yamamoto Takuto , Minami Naojiro , Ikeda Shuntaro , Honda Shinnosuke
Published: January 2025

MERVL (murine endogenous retrovirus with leucine tRNA primer) is expressed during zygotic genome activation (ZGA) in mammalian embryos. Here, we show that the Polycomb group ring finger 5 (Pcgf5), a key component of Polycomb repressive complex 1 (PRC1), forms a chimeric transcript with MT2C_Mm, one of the long terminal repeat sequences of MERVL. Knockdown ofPcgf5reduced developmental rates and decreased H3K27me3 and H2AK119ub1 modification during embryogenesis. In addition, not only genes expressed during ZGA but also imprinting genes were upregulated inPcgf5knockdown embryos. Moreover,Pcgf5was involved in the addition of the H3K27me3 modification to the maternalXistregion. This is the first report of a MERVL-regulated transcript regulatingXistexpression in mouse preimplantation embryos. Our results suggest that analysis of chimeric transcripts with MERVL will provide insight into the relationship between ZGA and noncanonical imprinting.
Motor cortical circuits are uniquely impacted by different exercise intensities
Authors: Harroum Nesrine , O’Farrell Amanda , Youssef Layale , Bohbot Louna , Maati Hajar , Joubert Marie , Pageaux Benjamin , Neva Jason L.
Published: January 2025

Acute aerobic exercise (AEX) can enhance motor learning and promote neuroplasticity. However, the effect of AEX intensity on primary motor cortex (M1) excitability has not been systematically examined. Hence, the dose-response relationship between AEX intensity and M1 excitability modulation remains unclear. This study investigated the impact of AEX intensity on distinct M1 circuits using transcranial magnetic stimulation (TMS). Thirty right-handed adults underwent four experimental sessions: rest (control), light (LIIT), moderate (MIIT), and high-intensity interval training (HIIT) AEX. AEX intensity was prescribed with the heart rate reserve (HRR) method, and the interval cycling sessions consisted of alternating between 3 min at the target intensity (LIIT: 35% HRR; MIIT: 55% HRR; HIIT: 80% HRR) and 2 min of active recovery (25% HRR) for 20 min total. We performed TMS measures before (Pre), immediately post (Post0), and 20 min post (Post20) AEX/rest to assess modulation of corticospinal excitability and GABAergic inhibition as measured by short interval-intracortical inhibition (SICI). This study found that: (1) HIIT and MIIT increased corticospinal excitability, with HIIT eliciting a sustained increase; and (2) all AEX intensities (LIIT, MIIT and HIIT) decreased SICI, with the greatest sustained reduction following MIIT. Also, there was a greater reduction in GABAergic inhibition when measured with anterior-posterior than posterior-anterior TMS current following MIIT. Collectively, our results demonstrate the impact of HIIT and MIIT to enhance corticospinal excitability and reduce GABAergic inhibition in M1. This study provides evidence for a dose-response effect of AEX intensity on the modulation of distinct motor cortical circuits.

KEY POINTS SUMMARY

Acute aerobic exercise (AEX) is known to modulate primary motor cortex (M1) excitability, but the effect of AEX intensity is unclear.

This study examined the impact of light-, moderate-, and high-intensity interval training (LIIT, MIIT, HIIT) AEX and rest (non-AEX, control) on distinct M1 cortical circuits using transcranial magnetic stimulation (TMS).

HIIT induced a sustained increase in M1 output excitability, MIIT induced a transient increase, and LIIT showed no effect.

All exercise intensities (LIIT, MIIT and HIIT) decreased GABAergic inhibition, as measured by short-interval intracortical inhibition (SICI), with MIIT showing a sustained decrease.

SICI measured with an anterior-to-posterior TMS current demonstrated greater GABAergic disinhibition compared to posterior-to-anterior TMS current following MIIT.

This study demonstrates a nuanced dose-response impact of AEX intensity on distinct M1 cortical circuits.
Movement path as an ethological lens into interval timing
Authors: Balcı Fuat , Hernandez Varsovia , Hoşer Ahmet , León Alejandro
Published: January 2025

Interval timing behavior is traditionally investigated in operant chambers based on the very focal responses of the subjects (e.g., head entry to the magazine, lever press). These measures are blind to the movement trajectory of the animals and capture only a tiny segment and some-times an idiosyncratic component of the animal’s behavior. In other words, the state of the temporal expectancy is not observable at every time point in the trial. On the other hand, in nature, temporal expectancies guide actions in a much more complex fashion. For instance, an animal might approach a food patch at different degrees as a function of the expected time of food availability (e.g., nectar collection behavior). The current study aimed to investigate interval timing in a more naturalistic fashion by analyzing the movement trajectory of rats infixed time(FT-30s) vs.variable time(VT-30s) schedules in modified open field equipment. We observed a temporally patterned movement inFTbut not in aVTschedule. In theFTschedule, rats moved away from the reward grid after consuming the presented water and were farthest from it for around 15 seconds, after which they started to approach the reward grid again. There was no such temporal patterning of movement trajectory in theVTschedule. Temporal control in theFTschedule was stronger in theWallcompared to theCentercondition. Our results show that movement trajectory may reflect instantaneous temporal expectancy.
LubriShieldTM- a unique permanent coating for indwelling urinary catheters that impedes surface-associated uropathogens from forming biofilm
Authors: Romero Ana I. , Surkov Serhiy , Wirsén Per , Brookes Graeme , Bergström Linda , Tejbrant Jan , Dhamo Elena , Wilks Sandra , Bryant Catherine , Andersson Jan
Published: January 2025

Catheter-associated urinary tract infection (CAUTI) is one of the most common healthcare-associated infections and biofilm formation plays a key role in its pathogenesis. Indwelling medical devices introduce ideal pathways inside the body for invading pathogens and feature surfaces conducive to biofilm development. These devices are the root cause of severe clinical infections often recalcitrant to antimicrobials. When bacteria and fungi switch to biofilm mode of growth, they produce a matrix in the form of extracellular polymeric substances (EPS). This creates a unique environment for growing virulent colonizers and persisting cells while also forming a shielding barrier against immune system attacks, antimicrobial agents and mechanical removal by fluid shear forces.

To address this challenge, LubriShieldTM- a novel permanent coating was invented, and evenly applied to both the internal and external surfaces of indwelling urinary Foley catheters. Without releasing active substances, it effectively prevented pathogens from producing biofilm. The coating was superhydrophilic and incorporated a proprietary anti-fouling ligand, which created a surface that significantly inhibited up to 99% of colonizing uropathogens from forming biofilm for the duration of use without any microbial killing (p< 0.001). The predominant uropathogens, including Gram-positive and Gram-negative as well as Candida albicans, were inhibited from forming biofilm on the LubriShieldTMcoated surfaces for up to 14 days in artificial urine medium. After challenging the adhering bacteria in a glass bladder flow model, the coating still significantly reduced biofilm formation by 83% (p<0.001).

The growth mode and emergent properties of adhering bacteria on uncoated silicone catheter surfaces were compared with those on LubriShieldTMcoated surfaces. RNA-seq analysis revealed that gene expression associated with microbial EPS formation was significantly downregulated on the coated surfaces. Additionally, microorganisms adhering to LubriShieldTMcoated catheters were 46% more susceptible to antibiotics compared to those on uncoated silicone catheters (p<0.01).