bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial dysfunction underlies monocyte immune deficiency in patients with severe alcohol-related hepatitis
Authors: Middleton Paul K. , Aramayo Ricardo J. , Montoya Alex , Shliaha Pavel V. , Pope Simon , Fets Louise , Vergis Nikhil , Thursz Mark R. , Cochemé Helena M. 
Published: January 2025

AbstractSevere alcohol-related hepatitis (sAH) is a life-threatening form of alcohol-related liver disease (ARLD) associated with a significant short-term mortality. Opportunistic infections due to impaired immune function are a major cause of patient mortality. Mitochondrial dysfunction within the liver is a well-recognised feature of ARLD and sAH. However, whether these hepatic mitochondrial defects extend to the immune system of sAH patients, underlying their immune dysfunction, remains unclear. Here, we demonstrate that sAH monocytes exhibit an increased content of inefficient, dysfunctional mitochondria. These changes were underpinned by abnormal mitochondrial cristae ultrastructure, which were associated with depletion of cristae structural proteins and alterations in cardiolipin profiles. Overall, our study uncovers novel structural and functional mitochondrial defects, which likely contribute to impaired monocyte immune function in sAH.
Females use multiple cues to assess competition for egg-laying decisions
Authors: Sharma Manvi , Ramesh Ashwini , Nagaraj Nisha , Isvaran Kavita 
Published: January 2025

AbstractAnimals deploy a wide suite of behavioural responses to reduce fitness costs related to competition. One common strategy is spatial avoidance of resource patches associated with high competition and this involves a need to accurately assess the level of competition associated with patches. Although well-studied in the context of predation risk (alarm cues vs kairomones), we lack in our understanding of how inputs from multiple types of cues are used for assessing the level of conspecific competition. We tested howAedes aegyptifemales select sites for oviposition when they encounter multiple types of cues from varying densities of conspecifics. We hypothesised that females perceive conspecific young within these sites as potential competition for their offspring, and tailor their response to the type and level of competition. Through binary choice trials, we assessed female oviposition behaviour in response to a gradient in two types of conspecific cues – egg and larvae. Our results indicate that female response was sensitive to the type of cue. Females showed attraction towards pools with low densities of both egg and larval conspecifics indicating conspecific cueing and the strength of response was stronger towards egg cues. However, this attraction response disappeared at high densities of conspecifics (both egg and larvae) suggesting that the resulting trade-off between benefits from conspecific cueing and costs of competition likely shapes oviposition site selection responses. The broad nature of the oviposition response was similar toward both egg and larval cues, but there were fine level differences in responses towards egg and larvae that depended on the conspecific density level. Our study shows that animals are under selection to use multiple cues to assess conspecific competition to minimise the costs of competition.
Sensory discrimination of chemical and temperature stimuli in the acoelSymsagittifera roscoffensis
Authors: Komarov Nikita , Aeschbacher Christopher , Sauterel Laurent , Zuercher Evan , Bailly Xavier , Martinez Pedro , Sprecher Simon G. 
Published: January 2025

AbstractEnvironmental cues provide critical sensory information for the survival of animals. Understanding how distinct sensory cues elicit or modulate certain behaviour thus provides insights into the neuronal adaptations to rapid and continuous changes in the surrounding world. Intertidal ecosystems are a particularly exposed to environmental fluctuations. Due to changing exposure to seawater, animals are subjected to continuous fluctuations of temperature or salinity during the course of day-night and tidal cycles. Animals in the intertidal environment show physiological and behavioural adaptations to these changes. When the acoelSymsagittifera roscoffensisis exposed to daylight during the tidal cycle, these animals are found at the surface of sandy beaches, which enhance the exposure of their photosynthetic algal (Tetraselmis convolutae) symbionts to light. Moreover,S. roscoffensisshows a strong positive phototactic displacement as well as both positive and negative geotaxis, both being evolved behavioural adaptations to enhance light-exposure for its photosymbiont. Currently little is known about other sensory systems and their functions inS. roscoffensis. In this study, we probe sensory capabilities ofS. roscoffensisfocusing on chemical and temperature cues. Our findings support thatS. roscoffensisshows avoidance behaviours to increased temperature and high salinity, preferring cooler environments with lower salinity.
Climatic niche conservatism in non-native plants depends on introduction history and biogeographic context
Authors: Rönnfeldt Anna , Holle Valén , Schifferle Katrin , Gallien Laure , Knight Tiffany , Weigelt Patrick , Craven Dylan , Cabral Juliano Sarmento , Zurell Damaris 
Published: January 2025

AbstractMany tools informing preventive invasion management build on the assumption that introduced species will conserve their climatic niches outside their native ranges. Previous research testing the validity of this assumption found contradictory results regarding niche conservatism vs. niche switching for non-native species. An open question is in how far these contradictions reflect context dependency, yet only few studies compared the niche dynamics of species introduced to multiple regions. Here, we used an ordination-based approach to quantify the climatic niche changes (stability, unfilling, expansion) of 316 plant species introduced to eight different regions across the world, including the Pacific region with extreme isolation between island groups. We then performed multiple phylogenetic regressions to assess how the regional context and species’ characteristics affect niche dynamics. Niche conservatism varied across regions, even within species. While niche expansion into previously unoccupied climates was generally low, niche unfilling varied strongly between regions. Generally, region-specific introduction history and species’ biogeographic attributes were more important for explaining niche changes than ecological traits. Niche expansion was consistently higher for species with small native range sizes, and niche stability increased. In contrast, niche unfilling decreased with time since introduction which could suggest that the lack of niche conservatism observed in many regions might be transient and potentially related to dispersal limitations. Overall, our results shed light on the context dependency of climatic niche changes when species are introduced to new regions, highlighting that the species and region-specific context should be accounted for when assessing the potential for niche changes.Significance StatementAs non-native species are introduced to new regions by humans, they may occupy the same climatic conditions as in their native ranges, leave parts of their native niche unfilled or expanding into previously unoccupied conditions. Knowing to which extent these niche dynamics generally occur is essential for understanding and managing biological invasions. Here, we evaluate regional differences in the climatic niche dynamics of non-native plants that were introduced to multiple regions across the world. We found marked variation across regions, influenced by factors such as the time that has passed since species were introduced, or biogeographic attributes of both the native and non-native ranges. These findings indicate that a lack of apparent niche changes is likely a temporary phenomenon.
Evolutionary potential of theEscherichia coliantimutator ΔnudJis reduced via altered mutational spectrum
Authors: Green R , Richards H , Ozbilek D , Tyrrell F , Barton V , Lovell SC , Gifford DR , Lagator M , McBain AJ , Krašovec R , Knight CG 
Published: January 2025

AbstractThe rate of spontaneous mutation is a key factor in determining the capacity of a population to adapt to a novel environment, for example a bacterial population exposed to antibiotics. Genetic and environmental factors controlling the mutation rate commonly also cause shifts in the relative rates of different mutational classes, i.e. the spectrum of spontaneous mutations. When the mutational spectrum is altered, the relatively enriched and depleted mutations may differ in their fitness effects. Here we aim to explore how a reduced mutation rate and altered mutational spectrum can contribute to adaptation inEscherichia coli. We measure mutation rates across a set of Nudix hydrolase deletants, finding multiple strains with an antimutator phenotype. We focus on the antimutator ΔnudJwhich can cause a 6-fold mutation rate reduction relative to the wildtype with an altered mutational spectrum. Not only doesnudJdeletion reduce the probability of antibiotic resistance arising but, in the case of rifampicin, the accessible resistance mutations under this altered mutation spectrum have greater fitness costs. While this effect is, so far, specific to this drug, it opens up the possibility of reducing the likelihood of resistance mutations establishing through simultaneous modification of mutation rate and spectrum. The identification and characterisation of antimutator alleles such as ΔnudJprovides potential targets for ‘antievolution drugs’ which could be applied during antibiotic treatment to inhibit NudJ activity. Such an approach could suppress spontaneous resistance evolution both through fewer resistance mutations and by limiting access to the fittest mutations.
multiHIVE: Hierarchical Multimodal Deep Generative Model for Single-cell Multiomics Integration
Authors: Nanduri Anirudh , Pavan Musale Krushna , Pandey Kushagra , Zafar Hamim 
Published: January 2025

AbstractMotivationRecently developed single-cell multiomics technologies are enhancing our understanding of cellular heterogeneity by providing multiple views of a biological system. CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) is one such multiomics assay, with the ability to connect cell states to functions by simultaneously profiling RNA and surface proteins from the same cell. However, the distinct technical characteristics of these data modalities pose significant challenges to their integration into a cohesive representation of cellular identity.ResultsHere we present multiHIVE, a hierarchical multimodal deep generative model for inferring cellular embeddings by integrating CITE-seq data modalities. multiHIVE employs hierarchically stacked latent variables as well as modality-specific latent variables to capture shared and private information from the modalities respectively, facilitating integration, denoising and imputation tasks. Extensive benchmarking using gold-standard real and simulated datasets demonstrates multiHIVE’s superiority in integrating CITE-seq datasets. Moreover, multiHIVE outperformed the state-of-the-art methods in imputing missing protein measurements and integration of CITE-seq dataset with unimodal dataset. Using a thymocyte development dataset, we showed that multiHIVE’s cellular embeddings can lead to improved trajectory inference and gene trend identification. Finally, using datasets across development and disease, we demonstrated that factorization of multiHIVE-inferred denoised expression into gene expression programs aids in identifying biological processes at multiple levels of cellular hierarchy.Availability and ImplementationmultiHIVE is implemented in Python and is publicly available athttps://github.com/Zafar-Lab/multiHIVE.
Visualizing sub-organellar lipid distribution using correlative light and electron microscopy
Authors: Lennartz H. Mathilda , Khan Suman , Böhlig Kristin , Leng Weihua , Elsner Falk , Scher Nadav , Wilsch-Bräuninger Michaela , Avinoam Ori , Nadler André 
Published: January 2025

AbstractLipids and proteins compartmentalize biological membranes into nanoscale domains which are crucial for signaling, intracellular trafficking and many other cellular processes. Studying nanodomain function requires the ability to measure protein and lipid localization at the nanoscale. Current methods for visualizing lipid localization do not meet this requirement. Here, we introduce a correlative light and electron microscopy workflow to image lipids (Lipid-CLEM), combining near-native lipid probes and on-section labeling by click chemistry. This approach enables the quantification of relative lipid densities in membrane nanodomains. We find differential partitioning of sphingomyelin into intraluminal vesicles, recycling tubules, and the boundary membrane of the early endosome, representing a degree of nanoscale organization previously observed only for proteins. We anticipate that our Lipid-CLEM workflow will greatly facilitate the mechanistic analysis of lipid functions in cell biology, allowing for the simultaneous investigation of proteins and lipids during membrane nanodomain assembly and function.
A cell-matrix interaction regulates the undifferentiated state and self-renewal capacity of avian primordial germ cells
Authors: Ichikawa Kennosuke , Motoe Yuzuha , Watanabe Tenkai , Ezaki Ryo , Matsuzaki Mei , Horiuchi Hiroyuki , McGrew Michael J. 
Published: January 2025

AbstractPrimordial germ cells (PGCs) are lineage restricted precursor cells of sperm and eggs. Whilst avian PGCs from chicken can be cultured and modified to produce genome-edited chickens, the long-term culture of PGCs from other bird species has not been achieved. Here, we explored the effects of a cell-matrix interaction on the in vitro propagation of chicken PGCs. Blocking integrin signaling severely reduced the self-renewal of the PGC, indicating that a PGC-matrix interaction is an essential process for self-renewal. We investigated the properties of somatic cell differentiated PGCs and expression analyses suggested that the PGCs undergo a partial epithelial-to-mesenchymal transition caused by excess PGC-matrix interactions. Finally, we conducted a long-term culture of chicken PGCs with matrix components, resulting in significant induction of their somatic conversion. These results suggested that a high level of PGC-matrix interaction can cause somatic conversion, whilst a moderate level is essential for their proliferation. Overall, we identified a molecular aspect of self-renewal and maintaining undifferentiated states of avian PGCs.
Enzymes can activate and mobilize the cytoplasmic environment across scales
Authors: Dindo Mirco , Metson Jakob , Ren Weitong , Chatzittofi Michalis , Yagi Kiyoshi , Sugita Yuji , Golestanian Ramin , Laurino Paola 
Published: January 2025

ABSTRACTBiomolecular condensates have so far been studied in terms of their structural, compositional, and functional properties. However, condensate enzymatic activity —a key aspect of cellular metabolism— remains unexplored due to the complexity of the system. In this study, using a combination of experimental, computational and theoretical techniques, we have discovered that the non-equilibrium activity which originates from catalytic reactions couples with the environment through various feedback mechanisms across five orders of magnitude of length scales. We observe that condensed enzymes catalyse more rapidly in the presence of crowding proteins and show that the increased enzymatic activity within these droplets stems from the emergence of lower-energy protein conformations induced by the highly crowded environment. Despite the crowding in the environment of the droplet, which might suggest an effective increase in its overall viscosity, we find that it becomes more agile, as evidenced by the observation of enhanced diffusion and macroscopic flow, due to the enzymatic activity. These findings shed new light on the dynamic interplay between enzymatic activity, composition and crowding in condensates, and their roles on the mobility and accessibility of various functional units in these environments, offering a novel perspective on liquidliquid phase separation in metabolically active conditions.
LncRNA SChLAP1 promotes cancer cell proliferation and invasion via its distinct structural domains and conserved regions
Authors: Oh Mihyun , Kadam Roshni Nagesh , Charania Zahra Sadruddin , Somarowthu Srinivas 
Published: January 2025

ABSTRACTLong non-coding RNAs (lncRNAs) play key roles in a range of biological processes and disease progression. Despite their functional significance and therapeutic potential, lncRNAs’ mechanisms of action remain understudied. One such lncRNA is the Second Chromosome Locus Associated with Prostate-1 (SChLAP1). SChLAP1 is overexpressed in malignant prostate cancer and is associated with unfavorable patient outcomes, such as metastasis and increased mortality. In this study, we demonstrated that SChLAP1 possesses distinct structural domains and conserved regions that may contribute to its function. We determined the secondary structure of SChLAP1 using chemical probing methods combined with mutational profiling (DMS-MaP and SHAPE-MaP). Ourin vitrosecondary structural model revealed that SChLAP1 consists of two distinct secondary-structural modules located at its 5’ and 3’ ends, both featuring regions with a high degree of structural organization. Ourin vivochemical probing identified potential protein-binding hotspots within the two modules. Overexpression of the modules led to a notable increase in cancer cell proliferation and invasion, proving their functional significance on the oncogenicity of SChLAP1. In conclusion, we discovered functionally important, independent modules with well-defined structures of SChLAP1. These results will serve as a guide to explore the detailed molecular mechanisms by which SChLAP1 promotes aggressive prostate cancer, ultimately contributing to the development of SChLAP1 as a novel therapeutic target.
Variability vs Phenotype: multimodal analysis of Dravet Syndrome Brain Organoids powered by Deep Learning
Authors: Turpin Isabel , Modrego Adriana , Martí-Sarrias Andrea , Haeb Anna-Christina , García-González Laura , Soriano Jordi , Ruiz Núria , Peñuelas-Haro Irene , Espinet Elisa , Tornero Daniel , Lao Oscar , Acosta Sandra 
Published: January 2025

ABSTRACTBrain organoids (BO) have risen as a reliable model for neurodelopmental disorders (ND), reproducing human brain development milestones. However, their significant intra- and inter-organoid variability compromises their use in advanced tasks such as drug testing. Overcoming experimental variability is crucial for models prone to variation, like unguided BO. BO modelling in Dravet Syndrome, a late-onset epileptic ND, represents a great challenge since BO variability accumulates with time, when phenotype shows in vitro. Leveraging deep learning, we developed ImPheNet, a predictive tool grounded in BO live imaging datasets. ImPheNet accurately classified phenotypes and assessed drug toxicity in BO derived from DS, revealing differences between genotypes and upon antiseizure drug exposure. These results are supported by transcriptomic and functional data, revealing an excitatory-inhibitory imbalance during the maturation of DS organoids. Altogether, our DL-predictive live imaging strategy, ImPheNet, emerges as a powerful tool enhancing BO research and advancing ND treatments.
Endurance training restores ageing-impaired lysosomal biogenesis factors in rest and response to acute exercise in rat skeletal muscle
Authors: Rajabi Hamid , Askari Benyamin , Clarke David C. 
Published: January 2025

AbstractLysosomes, crucial for autophagy, play a pivotal role in cellular processes influenced by exercise. This study investigates the impact of ageing on lysosomal function, focusing on Transcription Factor E3 and its regulators, mTORC1 and Calcineurin, emphasizing their response and adaptation to endurance training. Twenty-five male Sprague-Dawley rats were categorised into Young (2 months), Aged sedentary and Aged sedentary single session (18 months), Aged long-term trained, and Aged trained-single session (17 months). Changes in variables were explored concerning sarcopenia by Soleus muscle fibre diameter and number measured via Eosin & Hematoxylin, phosphorylated and total TFEB protein levels via western blot, mTORC1 and Calcineurin mRNA levels via real-time PCR. Ageing happened with increased pTFE3/TFE3totalprotein (BF=579) and declined mTORC1 mRNA (BF=3.99) and muscle diameter (BF=87), signifying sarcopenia and potential contributors. Conversely, Calcineurin mRNA (BF=0.67) and muscle fibre number (BF=0.31) remained unaltered during ageing. Endurance exercise induced acute responses, reducing pTFE3/TFE3totalprotein (BF=306) and elevating mTORC1 (BF=1.57) and Calcineurin mRNA levels (BF=3.19). Three weeks of endurance training further decreased resting pTFE3/TFE3totalprotein (BF=174) while increasing Calcineurin mRNA (BF=12), and muscle fibre diameter (BF=126), with no changes in mTORC1 mRNA levels (BF=0.46) and muscle fibre number. Post-exercise, trained rats sustained decreased pTFE3/TFE3totalprotein (BF=56) and elevated mTORC1 mRNA (BF=1.16). In conclusion, this study underscores the involvement of TFE3, MTORC1, and Calcineurin in sarcopenia, proposing endurance training as an effective strategy to mitigate age-related changes and enhance muscle function in aged rats. Additionally, it suggests impairments in TFE3 possibly contribute to sarcopenia in ageing.key pointGiven the pivotal role lysosomes play in multiple homeostatic processes, investigating mTORC1, Calcineurin, and TFE3, an overlooked lysosome biogenesis factor directly involved in the metabolic effects of exercise, could help understand the metabolic state of sarcopenia and the role exercise plays in it.Through eosin & hematoxylin, western blotting and real-time PCR, we found Aging results in Sarcopenia, reduced TFE3 activity and mTORC1 gene expression.We saw a single bout of exercise elicit a response by increasing TFE3 protein activation, mTORC1, and Calcineurin gene expression, which is directed to improved sarcopenia.Three weeks of exercise improved sarcopenia and was accompanied by elevated only with resting levels of TFE3 protein activation, and Calcineurin gene expression.Endurance training was still able to licit post exercise response in TFE3 protein activation, and Calcineurin gene expressionEndurance training is a beneficial remedy for sarcopenia, and TFE3 protein is a major crucial player in inducing its effects.