bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in intrinsic promoter strength underlies the temporal hierarchy of theCaulobacterSOS response induction
Authors: Kamat Aditya , Joseph Asha M. , Rathour Deeksha , Badrinarayanan Anjana 
Published: January 2025

AbstractBacteria encode for gene regulatory networks crucial for sensing and repairing DNA damage. Upon exposure to genotoxic stress, these transcriptional networks are induced in a temporally structured manner. A case in point is of the highly conserved SOS response thwat is regulated by the LexA repressor. Studies have proposed that affinity of LexA towards promoters of SOS response genes is the primary determinant of its expression dynamics. Here, we describe an additional level of regulation beyond LexA properties that modulates the SOS response gene expression pattern. Using transcriptomic analyses, we reveal a distinct temporal hierarchy in the induction of SOS-regulated genes inCaulobacter crescentus. We observe that LexA properties are insufficient in predicting the temporal hierarchy of these genes. Instead, we find that intrinsic promoter strength underlies the order of gene activation, with differential sigma factor association as a key factor in modulating gene expression timing. Our findings highlight a novel regulatory layer in SOS dynamics and underscore the importance of promoter properties in shaping bacterial stress responses.
Rapid catecholamine trafficking regulates neutrophil functions and neutrophil-platelet interactions
Authors: Mohr Jennifer , Schmitz Anne , Dinarvand Meshkat , Shankar Sangeetha , Hill Bjoern F. , Wulfert Franziska , Neubert Elsa , Shumanska Magdalena , Kaushik Sofia , Kartaschew Linda , Bogeski Ivan , Daniel James , Jung Sebastian , Eble Johannes , Erpenbeck Luise , Kruss Sebastian 
Published: January 2025

AbstractNeutrophils are key effector cells of the innate immune system that respond to small signaling molecules regulating immune responses. For a long time, similarities between neuronal and immune cells have been discussed. Here, we show that human neutrophils rapidly take up, package and use catecholamine neurotransmitters such as dopamine or epinephrine via the machinery known from neurons. Uptake and release of catecholamines as well as trafficking and packaging into MPO/VMAT2-positive primary vesicles is visualized with false fluorescent neurotransmitters. We also directly image the fast (> 10 s) and transient release of catecholamines from neutrophils with near infrared fluorescent nanosensors. Serotonin or activated platelets trigger calcium (Ca2+) signaling and consequently exocytosis of catecholamines. They reduce NET-formation but increase platelet aggregation. Thus, we establish similarities between neurons and neutrophils and identify a paracrine neutrophil-platelet feedback loop relevant for inflammatory and coagulatory conditions.
Non-Visual Light Sensing Enhances Behavioral Memory and Drives Gene Expression inC. elegans
Authors: Ji Zhijian , Wang Bingying , Chandra Rashmi , Liu Junqiang , Yang Supeng , Long Yong , Egan Michael , L’Etoile Noelle , Ma Dengke K. 
Published: January 2025

AbstractVisible light influences a range of physiological processes, yet how animals respond to it independently of the visual system remains largely unknown. Here, we uncover a previously undescribed light-induced transcriptional pathway that modulates behavioral plasticity inC. elegans, a roundworm without eyes. We demonstrate that ambient visible light or controlled-intensity visible-spectrum LED activates an effector genecyp-14A5in non-neuronal tissues through the bZIP transcription factors ZIP-2 and CEBP-2. Light induction ofcyp-14A5is more prominent at shorter wavelengths but is independent of the known blue light receptors LITE-1 and GUR-3 inC. elegans. This bZIP-dependent genetic pathway in non-neuronal tissues enhances behavioral adaptability and olfactory memory, suggesting a body-brain communication axis. Furthermore, we use the light-responsivecyp-14A5promoter to drive ectopic gene expression, causing synthetic light-induced sleep and rapid aging phenotypes inC. elegans. These findings advance our understanding of light-responsive mechanisms outside the visual system and offer a new genetic tool for visible light-inducible gene expression in non-neuronal tissues.
Optimized Detection and Inference of Names in scRNA-seq data
Authors: Tulyeu Janyerkye , Priest David , Wing James B. , Søndergaard Jonas Nørskov 
Published: January 2025

AbstractAccurate identification of immune cell subsets in single-cell (sc)RNA-seq data is critical for understanding immune responses in autoimmune diseases, infections, and cancer. One caveat of scRNA-seq is the inability to properly assign rare immune cell subsets due to gene dropout events. To circumvent this caveat, we here developed Optimized Detection and Inference of Names in scRNA-seq data (scODIN). scODIN uses an informed holistic two-step approach combining expert knowledge with machine learning to rapidly assign cell type identities to large scRNA-seq dataset. First, scODIN uses key lineage-defining markers to identify a set of core cell types. Second, scODIN compensates for dropout events by integrating a k-nearest neighbors (kNN) algorithm. We additionally programmed scODIN to detect dual and transitional phenotypes, which are usually overlooked in conventional analyses. Consequently, scODIN may enhance our understanding of immune cell heterogeneity and provides comprehensive insights into immune regulation, with broad implications for immunology and personalized medicine.
PID-controller enhanced artificialβ-cells
Authors: Liu Lin , Jacobson Bruna , Stefanovic Darko 
Published: January 2025

AbstractConventional management of diabetes via injection or external insulin pumps suffers from inconvenience and inability to accurately maintain blood glucose levels. A potential solution to these problems consists of implanting synthetic artificialβ-cells that can sense glucose and transcribe insulin protein. We focus on one such artificialβ-cell recently described in the work of Xie et al. Experimental results show these cells are able to release insulin and somewhat improve postprandial glucose levels in diabetic mice. However, they fail to achieve the degree of glucose regulation as in healthy mice. In our analysis, we explain that this artificialβ-cell system has a major disadvantage: it is a high-dimensional dynamic system but with little tuning space. Here, we propose a PID-controller-based enhanced artificialβ-cell design to solve this issue. Our results based on an analytical model and numerical simulations show that the computational method of PID-control can enhance engineered artificialβ-cells, such that they could perform better in regulating glucose levels in Type 1 diabetic mice compared with artificialβ-cells without PID-control: they could shut down the production of insulin in time and maintain a proper glycemia level, and there is more tuning space for artificialβ-cells with PID control.
Fitting multiple bacterial growth data using continued fraction of straight lines
Authors: Shruti I S , Vijay Prakash S 
Published: January 2025

AbstractThe growth of a population is the net result of growth and decline in the number of individuals over time. When the growth in number is more than the decline, the population is said to be growing and vice versa. In other words, the growth rate of a population is influenced by two opposing factors, a growth promoting factor and a growth restricting factor. In this work, we estimate growth rates by applying a biological growth model that is based on the continued fraction of straight lines with two parametersaandm. The parametersaandmrepresent nonlinear i.e. growth restricting and linear i.e. growth promoting parts of the model, respectively. To fit this model, we use a publicly available dataset that exhibits the growth of three different strains of bacteria depending on the concentration gradient of the antibiotic Tetracycline. We also propose a method to automatically estimate growth rates for large-scale applications. Finally, a growth coordinate system withaandmas the axes is used to interpret the estimations.
Progenitor Heterogeneity in the Developing Cortex: Divergent and Complementary Roles of NG2-Progenitors and RGCs
Authors: Ojalvo-Sanz Ana Cristina , Figueres-Oñate María , Barriola Sonsoles , Pernia-Solanilla Carolina , Sanchez-Gonzalez Rebeca , García Lina Delgado , López-Mascaraque Laura 
Published: January 2025

AbstractBrain development is a highly coordinated process that arises from a pool of neural progenitor cells (NPCs). Traditionally, research has largely focused on Radial Glial Cells (RGCs), which produce neurons and glia. However, recent findings revealed that the progenitor landscape is more complex and heterogeneous than previously understood. Emerging evidence indicates that NG2 glia, also known as oligodendrocyte precursor cells (OPCs), may contribute to generating other cell types, including neurons and astrocytes. This suggests that NG2 glia, or a specific subset, may act as multipotent NPCs, expanding their role in brain development beyond their known lineage.We explore the cellular, molecular, and functional differences between NG2- and GFAP- expressing progenitors (NG2-NPCs and GFAP-NPCs) across different developmental stages. Usingin-uteroelectroporation and StarTrack technology, we examined whether these progenitors represent distinct populations and analyzed how their differences influence their functional roles based on cell fate decisions. Our findings uncover functional divergence between NG2-NPCs and GFAP-NPCs, particularly regarding their cell fate decisions. While both populations contribute to the formation of neurons and glial cells, the progeny of NG2-NPCs and GFAP-NPCs differ markedly in their contributions to neurogenesis and gliogenesis. Further, we conducted a comprehensive transcriptomic analysis of NG2-NPCs and GFAP-NPCs to elucidate the molecular basis for these functional differences. This study demonstrates distinct gene expression profiles. While NG2-NPCs show enrichment for genes associated with neurogenesis and synaptic transport, GFAP-NPCs displayed upregulation of genes involved in progenitor cell maintenance. This indicates that each progenitor type is governed by distinct molecular programs, shaping their contributions to brain architecture and function. In summary, our findings underscore the divergent roles of NG2-NPCs and GFAP-NPCs in driving cellular diversity and functional maturation in brain development, providing new insights into how these progenitor populations contribute to neural diversity and brain function.Abstract Figure
The emergence of E-Cadherin spot junctions between germline and somatic cells facilitates late stage oogenesis inDrosophila
Authors: Weichselberger Vanessa , Balaji Ramya , Rodriguez-Franco Marta , Classen Anne-Kathrin 
Published: January 2025

ABSTRACTCoordinated tissue morphogenesis relies on precise interactions between distinct cell lineages. During development of theDrosophilaoocyte, interactions between di_erent somatic follicle cell types and the germline-derived nurse cells and the future oocyte are crucial for coordinating oogenesis. However, the molecular basis of their interaction throughout enormous morphological changes remains largely unexplored. During late oogenesis, nurse cells transfer their cytoplasmic content into the oocyte, while anterior follicle cells (AFCs) must closely envelop the nurse cells to induce phagoptosis and remove their remnants. We identify E-cadherin-based spot junctions as novel adhesive complexes at this essential soma-germline interface. AFCs reorganize their E-cadherin from intraepithelial adherens junctions to their apical surface to form interlineage spot junctions with nurse cells, representing a switch in adhesive and thus mechanical coupling. The distribution and density of these junctions is stably organized, even as the interface undergoes dramatic size changes. Additionally, we show that these junctions integrate into a microvilli-rich nurse cell surface, influencing microvilli architecture. Importantly, disruption of E-cadherin spot junctions impairs nurse cell enveloping. Our findings reveal a switch from intra-lineage to inter-lineage mechanical coupling that is driven by the formation of E-Cadherin spot junctions and highlights their essential role in ensuring robust soma-germline coupling and coordination during nurse cell dumping in late oogenesis.
Redefining catecholaminergic polymorphic ventricular tachycardia (CPVT) as a neurocardiac condition
Authors: O’Reilly Molly , Verkerk Arie , Remme Carol Ann 
Published: January 2025

AbstractCatecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterised by adrenergic activity-induced sudden cardiac death. It is most often caused by mutations in theRYR2gene encoding ryanodine receptor 2 (RyR2), which is essential for intracellular calcium handling. Research has traditionally focused on the consequences of mutations at the cardiomyocyte level. However, RyR2 is also expressed in neuronal tissue, and patients often present with clinical signs of autonomic dysfunction. Here, we assessed if there is a neuronal phenotype in this classically cardiac condition.Using the established CPVT mouse modelRyr2-R2474S, we found that RyR2 is abundantly expressed in stellate ganglia neurons (SGNs) - the adrenergic neurons that project directly to the myocardium and modulate heart function. We revealed that in isolatedRyr2-R2474S SGNs there is altered calcium homeostasis suggestive of intracellular calcium leakage, and increased neurite projections when maintained in culture. We furthermore showed that hearts ofRyr2-R2474S mice are sympathetically hyper-innervated, with an increased heterogeneity in innervation within the myocardium. This led to changes in the quantities of neurotransmitters and their metabolites within the heart, indicating increased norepinephrine turnover.CPVT may therefore be redefined as a neurocardiac disorder, with neuronal dysregulation being a prominent component of the disease. In addition to cardiomyocytes,RYR2mutations also affect stellate ganglia neuron function and cardiac innervation, with potential implications for arrhythmogenesis, risk stratification and therapy.Graphical abstractIn wildtype hearts, activation of sympathetic neurons leads to their release of norepinephrine (NE), which binds to beta adrenergic receptors (β-ARs) on the cardiomyocyte membrane. The resultant initiation of intracellular signalling cascades involving cyclic AMP (cAMP) leads to reduced inhibition of the sarcoendoplasmic reticulum (SR) calcium ATPase (SERCA) pump and consequent calcium overload in the SR. This triggers the opening of ryanodine receptor 2 (RyR2), causing SR calcium to be released into the cytoplasmic space resulting in a calcium wave which triggers contraction.In CPVT hearts, there is increased sympathetic neuron innervation of the ventricular myocardium. When cardiac sympathetic nerves are activated, there is an enhanced release of NE. This excess NE causes increased activation of β-ARs and an augmented intracellular cAMP response, which in turn leads to a greater reduction of the inhibition of SERCA, augmented SR calcium overload, and a heightened propensity for spontaneous calcium leakage to trigger a calcium wave, delayed afterdepolarisations, and arrhythmias.Figure created withBioRender.com.
MUSICiAn: Genome-wide Identification of Genes Involved in DNA Repair via Control-Free Mutational Spectra Analysis
Authors: Seale Colm , Barazas Marco , van Schendel Robin , Tijsterman Marcel , Gonçalves Joana P. 
Published: January 2025

AbstractMotivationUnderstanding the factors involved in DNA double-strand break (DSB) repair is crucial for the development of targeted anti-cancer therapies, yet the roles of many genes remain unclear. Recent studies show that perturbations of certain genes can alter the distribution of sequence-specific mutations left behind after DSB repair. This suggests that genome-wide screening could reveal novel DSB repair factors by identifying genes whose perturbation causes the mutational distribution spectra observed at a given DSB site to deviate significantly from the wild-type. However, designing proper controls for a genome-wide perturbation screen could be challenging. We explore the idea that a genome-wide screen might allow us to forgo the use of traditional non-targeting controls by reframing the analysis as an outlier detection problem, assuming that most genes have minimal influence on DSB repair.ResultsWe propose MUSICiAn (Mutational Signature Catalogue Analysis), a compositional data analysis method that ranks gene perturbation-specific mutational spectra without controls by measuring deviations from the central tendency in the distributions of all spectra. We show that MUSICiAn can effectively estimate pseudo-controls for the existing Repair-seq dataset, screening 476 genes and 60 non-targeting controls. We further apply MUSICiAn to a genome-wide dataset profiling mutational outcomes induced by CRISPR-Cas9 at three target sites across cells with individual perturbations of 18,406 genes. MUSICiAn successfully recovers known genes, highlights the spliceosome as a lesser-appreciated player in DSB repair, and reveals candidates for further investigation.Availabilitygithub.com/joanagoncalveslab/MUSICiAn.
The Plankton Imager (Pi-10): An imaging instrument for automated and continuous zooplankton data collection
Authors: Scott James , Pitois Sophie G. , Blackwell Robert , Close Hayden , Culverhouse Phil , Tilbury Julian 
Published: January 2025

ABSTRACTThe Pi-10 is the latest iteration of the Plankton Imager: a high-speed colour line-scan camera that images particles in a flow-through system. The Pi-10 is a cost-effective, easy to install and low maintenance automated instrument that can be used on any platform with access to water and power supply. We tested the Pi-10 on the research vessel Cefas Endeavour, connected to a continuous water supply pumping water at 34 L min-1. The instrument collected images of particles, within the size range of 180 µm - 3.5 cm, automatically and continuously, alongside other vessel operations, in all weathers over a period of 18 days. The Pi-10 successfully captured and saved up 5000 images per minute, translating into a 46 GB of digital storage per day. When particle density exceeded 147 per litre, the instrument stopped saving all images, while still recording the number of particles that passed through the system. This is akin to subsampling, with more sub-sampling required in areas or times of high particle density (e.g at the time of spring plankton bloom or in turbid waters). The Pi-10 collects high volumes of data in a continuous manner, thus providing unprecedented fine spatial data. The high frequency nature of the instrument opens the door to new areas of research. These include, in particular, the observation of fine scale processes, the move towards real-time sampling, and the increased capability to build a digital twin of the oceans. As technologies continue evolving the Pi-10 performance will increase, being able to collect and save more and more images.
Effects of host sex, age and behaviour on co-infection patterns in a wild ungulate
Authors: Berland Florian , Bourret Vincent , Peroz Carole , Malandrin Laurence , Bonsergent Claire , Bailly Xavier , Masseglia Sébastien , Nouvel Laurent-Xavier , Lagrée Anne-Claire , Rouxel Clotilde , Dimeglio Chloé , Izopet Jacques , Ollivier Valentin , Boulinier Thierry , Villena Isabelle , Aubert Dominique , Sluydts Vincent , Le Loc’h Guillaume , Bonnet Arnaud , Chaval Yannick , Merlet Joël , Lourtet Bruno , Gilot-Fromont Emmanuelle , Verheyden Hélène 
Published: January 2025

AbstractRecent zoonotic disease emergences reveal the importance of studying wildlife parasite communities. As wild hosts frequently harbour diverse parasite species, understanding the drivers of multiple infection patterns in free-ranging hosts is critical for elucidating the ecological and epidemiological dynamics of parasite communities. In this study, we analysed co-infection patterns in European roe deer (Capreolus capreolus) inhabiting a fragmented rural landscape in southwestern France. Using data from 130 GPS-tracked roe deer, we examined the influence of proximity to livestock, host activity levels, age, sex, and between-parasite interactions on the presence of 11 parasitic taxa. Hierarchical modelling of species communities (HMSC) revealed that proximity to livestock significantly increased the likelihood of infection with orofecally transmitted parasites (Toxoplasma gondii, gastrointestinal parasites). Sex and age were other key predictors, with males and juveniles exhibiting a higher frequency of parasite presence, likely influenced by hormonal and immune system differences. Activity levels showed distinct age-related effects, with higher activity levels being positively associated with increased parasite prevalence in yearlings, but not in adults. In contrast, parasite association patterns within individual hosts were weak, suggesting minimal interactions between parasite species. Our findings highlight the interplay between exposure and susceptibility in shaping co-infection patterns and underscore the value of hierarchical modelling approaches in multi-parasite systems.Key FindingsParasite communities, studied in 130 GPS monitored roe deer, revealed frequent co-infection.Proximity to livestock increased the risk of infection by parasite taxa shared with domestic animals.For several parasitic taxa, males and younger roe deer had a higher probability of infection.The effect of host activity on parasite infection was dependent on roe deer age.Only slight between-parasite interactions were detected within individual hosts.
Cell-state specific drug-responses are associated with differences in signaling network wiring
Authors: Krämer Niels , van Eijl Roderick , Stohn Tim , Tanis Sabine , Wessels Lodewyk , Bosdriesz Evert , Mulder Klaas W. 
Published: January 2025

AbstractIntracellular signaling pathways form networks through which information is transmitted, often in the form of kinase-mediated phosphorylation events, to interpret extracellular signals and elicit appropriate cellular responses. Yet, even isogenic cells in a homogenous environment show heterogeneity in their intracellular “cell-state”, as well as their response to extracellular signals. Here, we aimed to better understand this relation between these phenomena by investigating how information flows through the EGF-receptor centered network upon targeted drug treatment, and how this is affected by cell-to-cell-state differences. Using single-cell ID-seq, we profiled the cell-state and signaling activity of primary human epidermal stem cells by measuring 69 (phospho-)proteins upon inhibition of the Erk/MAPK (p90RSK) and Akt/mTOR (p70S6K) routes downstream of the EGF pathway. We found that the effects of drug treatment propagated from the EGF-signaling pathway to other connected parts of the cellular signaling network, indicating altered signaling flow. We identified nine distinct cell-states that show pervasive state-dependent drug-responses for many (phospho-)proteins. Computational modeling of the signaling network using single-cell Comparative Network Reconstruction showed that many interactions between phospho-proteins (i.e. network wiring) were quantitatively different between cell-states. Furthermore, (phospho-)proteins with a cell-state dependent drug response, were more likely to be involved in interactions that showed a cell-state dependent strength. Overall, our results indicate that drug treatment response and signaling interactions between proteins are closely related and modulated by cell-state.