bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid-solid coexistence at single fibril resolution during tau condensate ageing
Authors: Sahu Mahaprasad S. R. , Wei Jiapeng , Weitz David A. , Knowles Tuomas P. J. , Garai Kanchan 
Published: February 2025

AbstractAggregated fibrillar tangles of the microtubule-associated protein tau are a hallmark of Alzheimer’s disease. It is becoming increasingly clear that a key process that can trigger the formation of such tau tangles is the aberrant ageing of biomolecular condensates of tau formed via liquid-liquid phase separation. This ageing process affects the overall mechanical and structural properties of the condensates, but the molecular-level mechanisms by which aggregation takes place in the condensates have remained elusive. Here, by tracking individual tau molecules inside the condensates by single molecule microscopy we show that the ageing process is characterized by the co-existence of a growing solid phase of tau within a dense liquid phase. The liquid phase is increasingly confined to the pores of the growing fibril gel network, but maintains its initial viscosity. These findings add a spatial dimension to the ageing of condensates and demonstrate that spatial heterogeneity is a key feature of the liquid-to-solid transition of tau.
Spatio-temporal dynamics of M1and M2macrophages in a multiphase model of tumor growth
Authors: Lampropoulos Ioannis , Kevrekidis Panayotis , Zois Christos , Byrne Helen , Kavousanakis Michail 
Published: February 2025

AbstractThis study investigates the complex dynamics of vascular tumors and their interplay with macrophages, key agents of the innate immune response. We model the tumor microenvironment as a multiphase fluid, with each cellular population treated as a distinct, non-mixing phase. The framework also incorporates diffusible species that are critical for processes such as nutrient transport, angio-genesis, chemotaxis, and macrophage activation. Numerical simulations of our model show how phenotypic and spatial heterogeneity in the macrophage population arises and how such heterogeneity impacts a tumor’s growth dynamics. Finally, we propose an immunotherapeutic strategy based on the experimental agent vactosertib which promotes an anti-tumor macrophage phenotype. Our simulations demonstrate an increased density of anti-tumor macrophages over the period of a few months, followed by a relapse period where the tumor regains its original dynamics.
A self-assembling cross-protective antigen against multiple Gram-positive nosocomial pathogens
Authors: Kramarska Eliza , Romero-Saavedra Felipe , Squeglia Flavia , La Manna Sara , Sadones Oceane , Marasco Daniela , Berisio Rita , Huebner Johannes 
Published: February 2025

AbstractESKAPE pathogens are responsible for complicated nosocomial infections worldwide and are usually resistant to commonly used antibiotics in clinical settings. Among these bacteria, vancomycin-resistantEnterococcus faeciumand methicillin-resistantStaphylococcus aureusare the two most important Gram-positive pathogens for which alternative treatments and preventions are urgently needed. We previously designed a multi-presenting antigen, embedding the main epitope displayed by the AdcA protein ofE. faecium, that conferred protection against different Gram- positive pathogens both in passive and active immunization models. Here, we developed a new presentation strategy for this epitope, the EH-motif, based on a self-assembling peptide. Self- assembling peptides have been promising in the fields of material sciences, nanoscience, and medicine and have also potential in vaccine development, as they allow multiple presentations of the epitope and provide an ideal size for production and application. We show that this multi- presenting peptide, here Q11-EH, forms stable fibers of nanometric size. We also demonstrate that antibodies raised against Q11-EH mediate the opsonic killing of a wide-spectrum of Gram-positive pathogens, includingE. faecium,S. aureus,andE. faecalis. Our data indicate that multiple presentation strategies are a potent tool for vaccine antigen improvement and point to Q11-EH as a promising antigen for the development of novel cross-protective vaccines.
Targeting BRAF kinase fusions with pan-RAF and vertical MAPK inhibition
Authors: Turner Jacqueline A. , MacBeth Morgan , Bagby Stacey , Whitty Phaedra , Hartman Sarah , Simmons Dennis , Yacob Betelehem , Robinson William A. , Couts Kasey L. 
Published: February 2025

AbstractBRAFkinase fusions are a form of structural variation in the genome and are recurrent events in driver-negative melanomas. WhileBRAFfusions reproducibly conserve the kinase domain, there is genetic variability with 5’ gene partners and specificBRAFbreakpoints. We investigated how genetic diversity ofBRAFkinase fusions affects dimeric signaling and ERK activation. We overexpressedBRAFfusions with 5’ gene partners includingAGK, ZKSCAN1, ARMC10, PPFIBP2, andTRIM24and found fusion dependent signaling and inhibitor sensitivity. Despite the development of next generation RAF inhibitors, there was paradoxical ERK phosphorylation with multiple pan-RAF inhibitors, which was ameliorated in certainBRAFfusions with vertical RAF/MEK inhibition using trametinib and LY3009120. Collectively, we observed some fusion-dependent effects but also tumor growth suppression and resolution of paradoxical activation with vertical pathway inhibition.
Climate-Driven Reshuffling of Butterfly Communities: Body Size Declines and Community Homogenization in a Rapidly Warming Switzerland
Authors: Zografou Konstantina , Kati Vassiliki , Knop Eva 
Published: February 2025

AbstractClimate change has been reshaping natural communities by driving species to change their ranges in response to warming temperatures. In Switzerland, the rate of warming since 1950 has approached nearly double the global average, making these impacts important for community composition and ecosystem function. Using the Community Weighted Length Index (CWLI) as the body size estimator, previously extracted by museum specimens, we studied two decades of butterfly community data that have been inventoried by the Biodiversity Monitoring Switzerland program. We checked for deviations from the expectation of random trends in the CWLI using null models. We modeled the long-term patterns at each site and the overall long-term patterns through linear regression and mixed-effects models alongside the model of the relationship between wing length, elevation, and abundance. CWLI of Swiss butterfly assemblages dropped by 5.2% over two decades, suggesting that warmer temperatures are differentially affecting large-bodied species. While CWLI trends were significantly declining at most sites (73%), a subset of sites (27%) showed trends of increasing CWLI, sometimes associated with cooler microclimates either in forests or at higher elevation. Our results further indicate a progressive homogenization of butterfly communities, marked by smoother CWLI slopes and reduced CWLI range over time. These results underline complex relations of climate-driven range shifts with body-size dynamics and community restructuring, emphasizing the importance of understanding the processes to mitigate biodiversity loss in thermally sensitive ecosystems.
From Mechanistic Interpretability to Mechanistic Biology: Training, Evaluating, and Interpreting Sparse Autoencoders on Protein Language Models
Authors: Adams Etowah , Bai Liam , Lee Minji , Yu Yiyang , AlQuraishi Mohammed 
Published: February 2025

AbstractProtein language models (pLMs) are powerful predictors of protein structure and function, learning through unsupervised training on millions of protein sequences. pLMs are thought to capture common motifs in protein sequences, but the specifics of pLM features are not well understood. Identifying these features would not only shed light on how pLMs work, but potentially uncover novel protein biology––studying the model to study the biology. Motivated by this, we train sparse autoencoders (SAEs) on the residual stream of a pLM, ESM-2. By characterizing SAE features, we determine that pLMs use a combination of generic features and family-specific features to represent a protein. In addition, we demonstrate how known sequence determinants of properties such as thermostability and subcellular localization can be identified by linear probing of SAE features. For predictive features without known functional associations, we hypothesize their role in unknown mechanisms and provide visualization tools to aid their interpretation. Our study gives a better understanding of the limitations of pLMs, and demonstrates how SAE features can be used to help generate hypotheses for biological mechanisms. We release our code, model weights and feature visualizer.1
Do camera light traps for moths provide similar data as conventional funnel light traps?
Authors: Holzhauer Vivian , Böttger Dennis , Bodesheim Paul , Brehm Gunnar 
Published: February 2025

AbstractInsects are of crucial importance for terrestrial ecosystems but many populations decline rapidly. Conventional collecting methods are usually time-consuming, resulting in a low temporal, spatial and taxonomic resolution of data. Automated camera light traps (CLT) allow non-lethal monitoring of species-rich moths (Lepidoptera) and other nocturnal insects, but so far little is known about their performance compared to conventional collecting methods.By observing the behaviour of moths in previous field work, we hypothesized that CLT perform well in moth groups in which species tend to sit down quietly after approaching the lamp (such as Geometridae) but worse in moth groups in which species are persistently active (such as Sphingidae).We tested the performance of two CLTs, equipped with Sony alpha 7II (24 megapixel sensor) cameras that resulted in images with approx. 420 dpi resolution. The study was carried out in a forested area near Bielefeld in NW Germany for 196 nights in a row from April to September 2023, and photos were taken every two minutes during the night. All macromoths recognizable in the photos were identified and counted individually. We directly compared the data from the CLTs with moth samples obtained from conventional funnel light traps (FLTs) during 12 nights which were spread across the flight season.The resulting 420 dpi images from the CLTs allowed reliable species identification of all observed macromoths with only few exceptions due to technical problems. In direct comparison during 12 nights, CLTs recorded 39 species exclusively, FLTs recorded 48 species exclusively, and 53 species were recorded by both methods equally. During the whole sampling period of 196 nights in a row, a total of 225 moth species were recorded by CLTs. CLTs tended to record Geometridae better than FLTs whereas Sphingidae tended to be undersampled by the new method. Familes differed in the length to which they remained on the screen of the CLTs.Our study is the first to systematically compare the methods and it shows that CLTs perform overall very well. Results from CLTs differ to a certain extent from conventional trapping methods because they seem to perform worse in groups with highly active species and perform better in calmer groups like geometrid moths. CLTs are promising devices for insect monitoring since they deliver data with high resolution in time, space and taxonomy. The use of artificial intelligence (AI) for the analysis of images is intended as the next logic step.
Decoding the restriction of T cell receptors to human leukocyte antigen alleles using statistical learning
Authors: ElAbd Hesham , Mahdy Aya K.H. , Wacker Eike Matthias , Gretsova Maria , Ellinghaus David , Franke Andre 
Published: February 2025

AbstractConventional T cells recognize peptides presented by the human leukocyte antigen (HLA) proteins through their T cell receptors (TCRs). Given that thousands of HLA proteins have been discovered, each presenting thousands of different peptide antigens, decoding the cognate HLA protein of a TCR experimentally is a challenging task. To address this problem, we combined statistical learning methods with a unique dataset of paired T cell repertoires and HLA allele information for 6,794 individuals. This enabled us to discover 53,870 T cell receptor alpha (TRA) and 1,095,576 beta (TRB) clonotypes that were associated with 437 unique HLA alleles. The identified clonotypes were targeting prevalent infections,e.g.influenza, cytomegalovirus and Epstein-Barr virus. Utilizing these clonotypes, we developed statistical models that impute the carriership of common HLA alleles from the TRA- or TRB-repertoire. In conclusion, the identified allele-associated clonotypes encode the HLA fingerprints and the immune exposure history of individuals and populations.
TRPV1+ neurons promote cutaneous immunity againstSchistosoma mansoni
Authors: Inclan-Rico Juan M. , Stephenson Adriana , Napuri Camila M. , Rossi Heather L. , Hung Li-Yin , Pastore Christopher F. , Luo Wenqin , Herbert De’Broski R. 
Published: February 2025

AbstractImmunity against skin-invasive pathogens requires mechanisms that rapidly detect, repel or immobilize the infectious agent. While bacteria often cause painful cutaneous reactions, host skin invasion by the human parasitic helminthSchistosoma mansonioften goes unnoticed. This study investigated the role of pain-sensing skin afferents that express the ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) in the detection and initiation of skin immunity againstS. mansoni. Data show that mice infected withS. mansonihave reduced behavioral responses to painful stimuli and sensory neurons exposed from infected mice have significantly less calcium influx and neuropeptide release in response to the TRPV1 agonist capsaicin. Using both gain- and loss-of-function approaches, data show that TRPV1+ neurons are critical regulators ofS. mansonisurvival during migration from the skin into the pulmonary tract. Moreover, TRPV1+ neurons were both necessary and sufficient to promote proliferation and cytokine production from dermal γδ T cells as well as neutrophil and monocyte skin accumulation post-infection. These results suggest a model in whichS. mansonimay have evolved to inhibit TRPV1+ neuron activation as a countermeasure that limits IL-17-mediated inflammation, facilitating systemic dissemination and chronic parasitism.One sentence summaryThe parasitic helminthSchistosoma mansoniaverts IL-17-dependent protective immunity by suppressing skin-innervating TRPV1+ neurons.
Genome report: Genome sequence of the hibiscus mealybug,Nipaecoccus viridis(Newstead), an invasive pest of citrus
Authors: Liesenfelt Tracy , Markee Amanda , Demard Emilie P. , Diepenbrock Lauren M. , Mongue Andrew J. 
Published: February 2025

AbstractMealybugs are frequently known for being pest insects to both ornamental and large-scale agricultural crops. Yet despite their agricultural importance, the genomic resources for this group remain quite small. One such species is the hibiscus mealybug,Nipaecoccus viridis(Newstead) (Hemiptera: Coccomorpha: Pseudococcidae). This invasive mealybug species has recently expanded throughout Florida and has spread across the state. Genomic resources would provide a new means to better understand the invasive nature of this insect, and thus, we present the de novo genome assembly forNipaecoccus viridis. Our genome assembly is 289 Mb, in which 91.2% of this sequence assembled into 5 chromosomal scaffolds. We report 15,370 genes to be present within our genome. We found that repetitive elements in the genome accounted for 32.40% of the sequence. These statistics follow similar trends to other previously sequenced pseudococcid species.
Spectral STED microscopy improves spectral sensitivity with polarity-sensitive probes and enables correlative measurements of membrane order and anomalous lipid diffusion
Authors: Urbančič Iztok , Schneider Falk , Galiani Silvia , Sezgin Erdinc , Eggeling Christian 
Published: February 2025

AbstractMolecular plasma membrane organization and dynamics play an important role in cellular signalling. Advances in our understanding of the nanoscale architecture of the plasma membrane heavily rely on the development of non-invasive experimental methods, particularly of advanced fluorescence microscopy and spectroscopy techniques with high spatio-temporal resolution and sensitivity to local molecular properties. However, it remains difficult to combine several of them for a multimodal characterisation that would reduce the possibility of misinterpretations. Here, we integrated a spectral detector into a super-resolution stimulated emission depletion (STED) microscope, achieving three goals. First, we show that compared to the standard ratiometric detection using fixed bandpass filters, the spectrally resolved acquisition together with spectral fitting or phasor analysis improves the accuracy of experiments determining membrane lipid order with polarity-sensitive probes multifold. Secondly, we demonstrate that this acquisition scheme allows the use of such probes in combination with other dyes with overlapping spectra, enabling co-localisation of the membrane order maps with other cellular structures of interest, e.g. fluorescently labelled proteins. Finally, we correlate the obtained membrane lipid order with the anomalous trapped diffusion properties of a fluorescent sphingomyelin lipid analogue in the plasma membrane of living cells, as determined by STED fluorescence correlation spectroscopy, and highlight that some of the most apparent trapping sites locate at the boundaries of local ordered environments discernible by the introduced spectral STED microscopy. With additional measurements in model membranes and Monte-Carlo simulations we conclude that for sub-100 nm ordered environments uneven probe partitioning cannot by itself explain the trapping diffusion of SM in cells.
Shoot at Site: Advancingin plantatransformation, regeneration and gene-editing through a cascade of wounding-mediated developmental regulators
Authors: Kshetry Arjun Ojha , Ghose Kaushik , Alok Anshu , Devkar Vikas , Raman Vidhyavathi , Stupar Robert M. , Herrera-Estrella Luis , Zhang Feng , Patil Gunvant B. 
Published: February 2025

ABSTRACTDeveloping transgenic and/or gene-edited plants largely depends on tedious, lengthy, and costlyin vitroregeneration protocols. While plants have remarkable regeneration ability, not all species, genotypes or even explants exhibit the same transformation and regeneration potential underin vitroconditions. To tackle this bottleneck, we have developed a seamless and user-friendly system to induce transgenic and gene-editedde novomeristems via a synthetic cascade comprising a wound-induced regeneration pathway, plant developmental regulators (DRs) and gene-editing reagents.WOUND INDUCED DEDIFFERENTIATION 1 (WIND1)is used as a transcriptional regulator to control the expression of various DR genes throughENHANCER OF SHOOT REGENERATION 1 (ESR1)promoter. This cascade was strategically appliedin plantato the non-meristematic internode ofN. benthamianato induce meristematic activity and regeneratede novoshoots with knock-out mutations of thephytoene desaturase(PDS) gene. This synthetic toolkit was further applied successfully to tomato and soybean. This methodology offers a transformative approach to overcome barriers in plant biotechnology, potentially accelerating the generation of transgenic and gene-edited plants without reliance on conventional tissue-culture intermediates.
Pan-cell type continuous chromatin state annotation of all IHEC epigenomes
Authors: Daneshpajouh Habib , Moghul Ismail , Wiese Kay C , Libbrecht Maxwell W 
Published: February 2025

1AbstractUnderstanding the mechanistic basis of genetic disease requires annotating the regulatory elements in the human genome. To this end, the International Human Epigenome Consortium (IHEC) has generated thousands of epigenomic datasets—including ChIP-seq, DNase-seq, and ATAC-seq—that measure various biochemical activities in the genome, including transcription factor binding, histone modification, and DNA accessibility. Currently, the predominant methods for integrating these data sets to annotate regulatory elements are segmentation and genome annotation (SAGA) algorithms such as ChromHMM and Segway. The majority of annotations generated by these methods are cell type-specific. However, as the number of profiled cell types has grown into the thousands, using thousands of cell type-specific chromatin state annotations proves undesirable for many applications. Therefore, recently, researchers have sought a single unified annotation of regulatory elements across all cell types, known as a “pan-cell type” annotation. Here, we present a pan-cell type annotation that summarizes all IHEC epigenomes using the recently-developed method, epigenome-ssm. This pan-cell type annotation comprises 33 genome-wide chromatin state feature signal tracks, each of which captures a regulatory program driving genomic activity in one or more cell types. We show that these feature maps constitute an intuitive and visualizable summary of epigenomic data.
Context-specific interaction of the lipid regulator DIP-2 with phospholipid synthesis in axon regeneration and maintenance
Authors: Park Seungmee , Jin Yishi , Chisholm Andrew D. 
Published: February 2025

AbstractNeurons maintain their morphology over prolonged periods of adult life with limited regeneration after injury.C. elegansDIP-2 is a conserved regulator of lipid metabolism that affects axon maintenance and regeneration after injury. Here, we investigated genetic interactions ofdip-2with mutants in genes involved in lipid biosynthesis and identified roles of phospholipids in axon regrowth and maintenance. CEPT-2 and EPT-1 are enzymes catalyzing the final steps in thede novophospholipid synthesis (Kennedy) pathway. Loss of function mutants ofcept-2orept-1show reduced axon regrowth and failure to maintain axon morphology. We demonstrate that CEPT-2 is cell-autonomously required to prevent age-related axonal defects. Interestingly, loss of function indip-2led to suppression of the axon regrowth phenotype observed in eithercept-2orept-2mutants, suggesting that DIP-2 acts to counterbalance phospholipid synthesis. Our findings reveal the genetic regulation of lipid metabolism to be critical for axon maintenance under injury and during aging.Article SummaryLittle is known about how adult neurons live long with limited regenerative capacity. This study investigates the role of lipid metabolism in sustaining neuronal health inC. elegans.Mutating phospholipid synthetic genes impairs axon regrowth after injury. Lack of DIP-2, a lipid regulator, restores regrowth, suggesting DIP-2 counterbalances phospholipid synthesis. Moreover, neuronal phospholipid synthesis is essential for preventing age-dependent axonal defects. These findings reveal phospholipid biosynthesis is key to axon integrity during aging and injury. As lipid metabolism is implicated in neurological disorders, this study serves as an entry point into investigating neuronal lipid biology under various conditions.