bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic insights intoPlasmodium vivaxandPlasmodium simiumhost shifts in Latin America
Authors: Lefebvre Margaux J. M. , Degrugillier Fanny , Arnathau Céline , González Camila , Rondón Silvia , Link Andrés , Chaves A. , Benavides Julio A. , Campos Aline Alves Scarpellini , dos Santos Edmilson , Huff Rosana , Silva Cláudia Maria Dornelles , Vanderhoeven Ezequiel , De Thoisy Benoit , Fontaine Michael C. , Prugnolle Franck , Rougeron Virginie 
Published: December 2024

AbstractPlasmodium vivaxcauses >70% of malaria cases in Latin America. The emergence ofPlasmodium simium, transmitted from humans to monkeys, increased the malaria burden, notably after an outbreak in 2015 in Brazil. To investigateP. simiumevolutionary history, we screened 646 monkey samples and analyzed whole genome variations for 19P. simiumand 408P. vivaxisolates.P. vivaxstrains were identified in Colombian (n=3) and Brazilian monkeys (n=1), suggesting host reinvasion in Colombia and genetic exchange betweenP. vivaxandP. simiumin Brazil. Genetic analysis indicates thatP. simiumoriginated from a host jump approximately a century ago, possibly linked toP. vivaxmigration from Mexico to Brazil. Genome-wide scans identified selection in genes interacting with primate hosts and vectors. These findings highlightP. simiumevolutionary history and zoonotic malaria risks, and underscore the need to include monkeys in malaria prevention measures while ensuring human-wildlife coexistence.
Prefrontal gamma oscillations and fear extinction learning require early postnatal interneuron-oligodendroglia communication
Authors: Plaisier Fabrice , Ibaceta-González Cristóbal , Khelfaoui Hasni , Watson Adrianne E S , Poilbout Corinne , Voronova Anastassia , Angulo María Cecilia 
Published: December 2024

AbstractEmerging evidence links oligodendrocyte (OL) lineage cells and myelin to cognitive processes, yet the role of myelination in shaping neuronal networks critical for cognitive tasks remains unknown. We demonstrate that early postnatal GABAergic signaling between interneurons and oligodendrocyte precursor cells (OPCs) is crucial for myelination of parvalbumin (PV) interneurons, which facilitatesin vivolow-gamma oscillations in the medial prefrontal cortex (mPFC) and supports fear extinction learning. Disruption of this signaling resulted in PV interneuron dysmyelination, decreased low-gamma power, and impaired tone fear extinction. These deficits were specific to PV interneuron dysmyelination, as overall mPFC myelination, high-gamma oscillations and context fear extinction remained unaffected. Increasing PV interneuron activity or enhancing myelination did not reverse the deficits, indicating the long-term consequences of these early myelination impairments. Our findings reveal critical roles of OPC GABAergic signaling in PV interneuron myelination and mPFC circuit maturation, with lasting impacts on gamma rhythms and cognitive function.
Heat stress drives rapid viral and antiviral innate immunity activation in Hexacorallia
Authors: Sharoni Ton , Becerra Adrian Jaimes , Lewandowska Magda , Aharoni Reuven , Voolstra Christian R. , Fine Maoz , Moran Yehu 
Published: December 2024

AbstractThe cnidarian class Hexacorallia, encompassing stony corals and sea anemones, plays a critical role in marine ecosystems. Coral bleaching, the disruption of the symbiosis between stony corals and zooxanthellate algae, is driven by climate change-induced seawater warming and further exacerbated by pathogenic microbes. However, how pathogens, especially viruses, contribute to accelerated bleaching remains poorly understood. The present study utilizes the model sea anemoneNematostella vectensisto explore these dynamics by creating a transgenic line with a reporter gene regulated by sequences from two RIG-I-like receptor (RLR) genes involved in antiviral responses. Under heat stress, the reporter gene showed significant upregulation, indicating that these regulatory sequences are indeed responsive to thermal stress. Analyses of transcriptome data ofN. vectensis,Exaiptasia diaphana(another sea anemone), and the stony coralStylophora pistillatarevealed stress-induced activation of a set ofbona fideimmune-related genes conserved between the three species. Population-specific differences in stress-induced transcriptional responses of immune-related genes were evident in bothNematostellaandStylophora, depending on geographic origin. InExaiptasia, the presence or absence of zooxanthellae also influenced stress-induced immune gene expression. To test whether the viruses themselves may contribute to this immune response under stress, we subjectedNematostellapolyps to variable periods of heat stress and measured the transcript levels of resident viruses as well as selected antiviral genes. While the antiviral genes responded within 1-3 hours of heat stress, viral gene expression was already upregulated within 30 minutes, suggesting that their increase might be contributing to the elevated immune response under stress, and consequentially, the further demise of organismal homeostasis. These findings highlight the complex interplay between environmental stress, viruses, immune responses, and symbiotic states in Hexacorallia. Better understanding of these mechanisms could provide insights into the role of immune pathways in coral resilience and bleaching in a changing climate.
Prevalence of AI findings on Chest X-ray in patients with lung cancer: a cross-sectional cohort study
Authors: Bramley Rhidian , Broadhurst Philip , Sharman Anna , Robert Dennis , Weber Elodie , Simon Marcus , Nasser Rehan , Brown Louise , Grudy Seamus , Evison Matthew 
Published: December 2024

AbstractBackgroundChest X-ray Radiography (CXR) is the primary investigation for patients with potential symptoms of lung cancer in the UK. Artificial intelligence (AI) can detect abnormalities on CXR and prioritise cases for reporting. We describe a method to determine which AI findings are associated with lung cancer to inform and validate prioritisation strategies.MethodsThis multicentre study compared the prevalence of AI findings on CXR in a retrospective cohort of patients diagnosed with lung cancer (4408 CXR) to the prevalence of AI findings in a prospective cohort of CXR from the referral population (107,065 CXR). Nineteen AI findings were assessed individually and in combination.ResultsThe most common AI findings in patients with lung cancer compared to the referral population were ‘Abnormal’ (92.6% vs 60.9%), Opacity (83.4% vs 45.4%), Consolidation (36.9% vs 12.9%), Atelectasis (33.5% vs 20.9%) and Nodule (32.7% vs 10.9%). The finding most associated with cancer based on the prevalence ratio in the cancer and referral cohorts were ‘Lung nodule malignancy’ (13.3), Cavity (4.0), Tracheal deviation (3.1), Nodule (3.0) and Consolidation (2.9). The percentage of CXR classed as ‘AI Abnormal’ varied by the referral cohort, 63.5% from Accident & Emergency vs 43.0% from General Practice. This suggests significant variation in the complexity of cases across referral pathways.ConclusionIndividual AI findings had limited sensitivity in detecting lung cancer. Using combinations of AI findings significantly improved cancer detection rates but required prioritising a larger proportion of CXR from the referral population.Key messagesWhat is already known on this topicThe National Institute for Clinical Excellence (NICE) early value assessment of “Artificial intelligence-derived software to analyse CXR for suspected lung cancer in primary care referrals” has identified the need for more research on the ability of AI to identify normal and abnormal findings on CXR to enable prioritised reporting of and speed up the cancer pathway.What this study addsThis study describes a method that sites deploying AI can use to determine the relative prevalence of AI finding on CXR in patients with lung cancer and in the referral population. The results indicate that prioritisation approaches focusing on single abnormalities such as lung nodule detection will miss most lung cancers on CXR.How this study might affect research, practice or policyPrioritisation strategies need to optimise the detection of lung cancer and other significant pathology. Using AI to prioritise abnormal CXR requires ethical consideration as moving some patients to the front of the reporting queue can also have a detrimental effect on patients that are not prioritised. This study indicates a range of AI findings need to be prioritised to maximise the detection rate of lung cancer.
Hormone-regulated dynamics of mRNA distribution on ribosomes in Sertoli cells
Authors: Leray Xavier , Morales Julia , Tréfier Aurélie , León Kelly , Bourquard Thomas , Musnier Astrid , Pecnard Emmanuel , Drobecq Lucile , Boulben Sandrine , Azzopardi Nicolas , Coulaud Rémi , Ouchène Hamza , Jaszczyszyn Yan , Reiter Eric , Guillou Florian , Pellissier Lucie P. , Poupon Anne , Yvinec Romain , Crépieux Pascale 
Published: December 2024

AbstractThe effects of hormone stimulation on the cell translational profile remain poorly understood. Here, using polysome profiling combined to RNA sequencing, we analyzed the translational response to follicle-stimulating hormone (FSH) of primary rat Sertoli cells, that exhibit an active anabolic activity regulated by reproductive hormones in the male gonad. We first established that mRNA distribution to polysomes follows a bimodal pattern, with 15% of mRNAs enriched in polysomes and exhibiting high expression. Critically, this basal polysomal enrichment had a major impact on FSH-induced mRNA recruitment to the polysomes, since FSH stimulation promoted the release of polysome-enriched mRNAs, while mRNAs that were the least associated to polysomes were preferentially recruited to polysomes upon stimulation. The FSH signal did not alter the core biological functions of Sertoli cells, but shifted the proteins involved in these functions, suggesting a molecular rewiring of the FSH-induced gene expression. These findings underscore how ribosomal reallocation dynamically adapts the cellular translatome to microenvironmental changes, enabling cells to fine-tune protein production in response to external stimuli.GRAPHICAL ABSTRACTBullet points• In Sertoli cells, most mRNAs distribute similarly between monosomes and polysomes, but a sub-population is specifically enriched in polysomes• Basal polysomal enrichment level has a major impact on FSH-induced mRNA recruitment or release from the polysomes• The FSH signal induced a global rewiring of the proteins involved in Sertoli cell basal activity• FSH-induced reassignment of ribosomes to specific mRNAs has to comply with a tightly maintained mRNA distribution landscape
SOD1 controls neutrophil oxidative burst and microbial killing
Authors: Brinkmann Volker , Goosmann Christian , Meier Andre , Majer Thomas , Foti Alessandro 
Published: December 2024

AbstractNeutrophils are immune cells specialized in producing large amounts of reactive oxygen species (ROS) to kill microbes. However, the mechanisms by which these cells regulate the balance of different ROS species and mitigate oxidative stress remain unclear. Here, we demonstrate that superoxide dismutase 1 (SOD1) plays a crucial role in ROS formation and antimicrobial activity in neutrophils. Our findings reveal that SOD1 modulates the ratio of superoxide (O2-) to hydrogen peroxide (H2O2) during the ROS burst, thereby supporting myeloperoxidase (MPO) enzymatic activity. By employing biochemical, cell biological, and genetic approaches, we show that SOD1 is crucial for ROS formation during NETosis and microbial infections, as it reduces oxidative stress and enables complete neutrophil activation. Impairment of SOD1 activity increases cysteine oxidation and lipid peroxidation. Neutrophils isolated from a patient with a SOD1 mutation exhibit decreased ROS production and impaired neutrophil extracellular trap (NET) formation. Our findings suggest that SOD1 is a novel regulatory factor in the oxidative burst that enables the full immunological response of neutrophils.
PI3Kγ pathway contributes to neuroinflammation and neuronal death induced by Zika virus infection
Authors: Teixeira Danielle Cunha , Campolina-Silva Gabriel , Marim Fernanda Martins , Santos Felipe Rocha da Silva , Queiroz-Junior Celso Martins , Costa Pedro Augusto Carvalho , Tana Fernanda de Lima , Costa-Souza Luiz Pedro , Pimenta Jordane Clarisse , Carvalho Júlia Gomes , Beltrami Vinícius Amorim , Rocha Felipe Emanuel Oliveira , Vieira Drielle Viana , Dornelas Evandro Gonçalves , Ferreira Giovana Cougo , Dias Felipe Ferraz , Guimarães Pedro Pires Goulart , Ribas Vinícius Toledo , Teixeira Antonio Lucio , Miranda Aline Silva de , Teixeira Mauro Martins , Souza Daniele da Glória , Costa Vivian Vasconcelos 
Published: December 2024

ABSTRACTZika virus (ZIKV) is an emerging arbovirus belonging to the Flaviviridae family and Orthoflavivirus genus, with a pronounced tropism for the central nervous system (CNS), where it induces neuroinflammation and neuronal death. ZIKV is known to exploit host cellular mechanisms, including the activation of survival pathways such as the PI3K/AKT signaling cascade, to evade apoptosis and enhance its replication. The phosphatidylinositol 3-kinase γ (PI3Kγ) pathway regulates critical cellular processes, including differentiation, recruitment, and survival, and is abundantly expressed in both brain tissue and leukocytes. This study aimed to investigate the role of the PI3Kγ pathway during ZIKV infection. Primary neuronal cultures from PI3Kγ-deficient mice (PI3Kγkd/kd) and human neuroblastoma SH-SY5Y cells treated with the PI3Kγ inhibitor AS605240 were infected with ZIKV to assess the impact of PI3Kγ signaling on viral replication and neuronal survival. Additionally, interferon α/β receptor knockout (A129) mice were treated with AS605240 either before or after ZIKV infection to evaluate the pathway’s role in neuroinflammation. In vitro, both genetic ablation and pharmacological inhibition of PI3Kγ suppressed ZIKV replication and prevented neuronal death. In vivo, mice treated with the PI3Kγ inhibitor exhibited enhanced protection against ZIKV infection, characterized by reduced viral load, and diminished brain and optic nerve damage. This neuroprotective effect correlated with altered astrocyte and microglia activation, marked by reduced TNF production in microglia. Furthermore, inhibition of PI3Kγ curtailed the recruitment and activation of CD8+ T cells and decreased the production of pro-inflammatory mediators, including IFN-γ and IL-17, in the brains of ZIKV-infected mice. These findings suggest that PI3Kγ activation facilitates ZIKV infection and exacerbates neuroinflammation. Pharmacological inhibition of the PI3Kγ pathway may offer therapeutic benefits by limiting viral replication and alleviating neuroinflammatory responses during ZIKV infection.
An improved neural network model enables worm tracking in challenging conditions and increases signal-to-noise ratio in phenotypic screens
Authors: Weheliye Weheliye H , Rodriguez Javier , Feriani Luigi , Javer Avelino , Uhlmann Virginie , Brown André EX 
Published: December 2024

AbstractHigh-resolution posture tracking ofC. eleganshas applications in genetics, neuroscience, and drug screening. While classic methods can reliably track isolated worms on uniform backgrounds, they fail when worms overlap, coil, or move in complex environments. Model-based tracking and deep learning approaches have addressed these issues to an extent, but there is still significant room for improvement in tracking crawling worms. Here we train a version of the DeepTangle algorithm developed for swimming worms using a combination of data derived from Tierpsy tracker and hand-annotated data for more difficult cases. DeepTangleCrawl (DTC) outperforms existing methods, reducing failure rates and producing more continuous, gap-free worm trajectories that are less likely to be interrupted by collisions between worms or self-intersecting postures (coils). We show that DTC enables the analysis of previously inaccessible behaviours and increases the signal-to-noise ratio in phenotypic screens, even for data that was specifically collected to be compatible with legacy trackers including low worm density and thin bacterial lawns. DTC broadens the applicability of high-throughput worm imaging to more complex behaviours that involve worm-worm interactions and more naturalistic environments including thicker bacterial lawns.
Discovery and Biosynthesis of Nyuzenamides D and E by Genome Mining inStreptomyces hygroscopicus
Authors: Lum Kah Yean , Kumar Rohitesh , Yang Zhijie , Souza Luciano D. O. , Jarmusch Scott A. , Moreira José M. A. , Morth Jens Preben , Ding Ling 
Published: December 2024

ABSTRACTNyuzenamides belong to the class of bioactive cinnamoyl moiety containing non-ribosomal peptides (NRPs). However, their biosynthetic gene cluster (BGC) remains unconfirmed. Genome-mining revealed a putativenyuBGC inStreptomyces hygroscopicusDSM 40578. Nyuzenamides D (1) and E (2) were subsequently isolated, and the structures were elucidated by detailed NMR spectroscopic and MS spectrometric data analyses. The absolute configuration of1was determined by a single-crystal X-ray diffraction study. Through retro-biosynthesis and CRISPR-genome editing, the non-ribosomal peptide synthetase biosynthetic gene cluster for nyuzenamides was confirmed. Our discovery enriches the diversity of cinnamoyl-containing nonribosomal peptides and validates the biosynthetic gene clusters for future genome-mining research.
A simple method to efficiently generate structural variation in plants
Authors: Bechen Lindsey L. , Ahsan Naiyara , Bahrainwala Alefiyah , Gehring Mary , Satyaki PRV 
Published: December 2024

AbstractPhenotypic variation is essential for the selection of new traits of interest. Structural variants, consisting of deletions, duplications, inversions, and translocations, have greater potential for phenotypic consequences than single nucleotide variants. Pan-genome studies have highlighted the importance of structural variation in the evolution and selection of novel traits. Here, we describe a simple method to induce structural variation in plants. We demonstrate that a short period of growth on the topoisomerase II inhibitor etoposide induces heritable structural variation and altered phenotypes inArabidopsis thalianaat high frequency. Using long-read sequencing and genetic analyses, we identified deletions and inversions underlying semi-dominant and recessive phenotypes. This method requires minimal resources, is potentially applicable to any plant species, and can replace irradiation as a source of induced large-effect structural variation.
Advances in magnetic particle imaging: evaluating magnetic microspheres and optimized acquisition parameters for high sensitivity cell tracking
Authors: Flood Samantha N. , Foster Paula J. 
Published: December 2024

AbstractMotivationThe sensitivity and resolution of magnetic particle imaging (MPI) depend on the choice of tracer and specific imaging parameters. For cell tracking applications with MPI, both the superparamagnetic iron oxide (SPIO) tracer and the cell labeling efficiency have a significant impact on MPI sensitivity and vary for different tracers.ObjectiveThis study compared three commercially available SPIO tracers (VivoTrax, Synomag-D and ProMag) and SPIO-labeled cells using magnetic particle relaxometry (MPR) and imaging. Further, the effect of imaging parameters (gradient field strength and drive field amplitude) on MPI signal strength, resolution, and cell detection limits, was evaluated.ResultsThe peak MPI signal measured by MPR was much higher for Synomag-D compared to VivoTrax and ProMag. However, the signal for intracellular Synomag-D was significantly reduced. In contrast, the signal for ProMag, a micron-sized iron oxide (MPIO) particle, was not significantly different for free and intracellular particles. The cellular iron loading was higher for ProMag compared to Synomag-D. The total MPI signal measured from images of free and intracellular SPIOs was highest for ProMag. Varying imaging parameters confirmed that a lower gradient field strength and higher drive field amplitude improved tracer and cellular sensitivity.ConclusionThese results show that the evaluation of tracers by MPR is not sufficient to predict the performance of all SPIO tracers; in particular, not for larger, polymer-encapsulated iron particles such as ProMag, or for SPIO tracers internalized in cells. Improvements in MPI sensitivity through lower gradient field strength and higher drive field amplitudes are associated with a trade-off in image resolution.
Discovery of a Potent and Selective Inhibitor of Human NLRP3 with a Novel Binding Modality and Mechanism of Action
Authors: Wilhelmsen Kevin , Deshpande Aditi , Tronnes Sarah , Mahanta Maitriyee , Banicki Matthew , Cochran Mary , Cowdin Samantha , Fortney Kristen , Hartman George , Hughes Robert , Montgomery Rusty , Portillo Claudia , Rubin Paul , Wang Yan , Yan Shijun , Morgan Barry A , Duisembekova Assem , Riou Romane , Marleaux Michael , Hochheiser Inga V. , Buthmann Hannes , Ferber Dominic , Wang Wei , Cranston Melanie , McKee Chloe M. , Mawhinney Thea , McKay Emma , Py Bénédicte F. , Geyer Matthias , Coll Rebecca C. 
Published: December 2024

ABSTRACTThe NLRP3 inflammasome is an intracellular protein complex that causes inflammation via the release of IL-1β and pyroptosis. NLRP3 activation is associated with many age-related inflammatory diseases, and NLRP3 inhibition is a promising therapeutic strategy. We previously performed a DNA encoded library screen to identify novel NLRP3 binding molecules. Herein we describe the characterization of BAL-0028 as a potent and specific inhibitor of NLRP3 signaling. Notably, BAL-0028 is a poor inhibitor of mouse NLRP3 but inhibits human and primate NLRP3 with nanomolar potency. Using cellular and biochemical analyses we demonstrate that BAL-0028 binds to the NLRP3 NACHT domain at a site that is distinct from the MCC950 binding pocket. Using humanized NLRP3 mice we show that a derivative of BAL-0028 inhibits NLRP3 activationin vivoin a peritonitis model. Finally, we demonstrate that BAL-0028 inhibits select hyperactive NLRP3 mutations associated with autoinflammatory diseases more potently than does MCC950. BAL-0028 thus represents a new modality for NLRP3 inhibition in inflammatory diseases.SUMMARYNLRP3 is a target for anti-inflammatory therapies and can be inhibited by the tool compound MCC950. We describe the characterization of a new small molecule inhibitor of NLRP3 BAL-0028 that has a distinct mechanism of action and binding site.
Exploration of mScarlet for development of a red lifetime sensor for calcium imaging
Authors: van der Linden Franka H. , Gadella Theodorus W.J. , Goedhart Joachim 
Published: December 2024

AbstractThe past decades, researchers have worked on the development of genetically encoded biosensors, including over 60 genetically encoded calcium indicators (GECIs) containing a single fluorescent protein (FP). Red fluorescent GECIs provide advantages in terms of imaging depths and reduced cell toxicity. Most of GECIs respond with a fluorescence intensity change, and researchers have strived to improve the sensors in terms of brightness and fold-change. Unfortunately, fluorescence intensity is influenced by many factors other than the desired sensor response. GECIs with a fluorescence lifetime contrast overcome this drawback, but so far, no bright red GECI has been developed that shows a fluorescence lifetime contrast. We tried to tackle this challenge by using the brightest red fluorescent proteins from the mScarlet family to develop a new sensor. We did succeed in creating remarkable bright probes, but the fluorescence lifetime contrast we observed in bacterial lysates was lost in mammalian cells. Based on our results, and the success of others to develop a pH and a voltage sensor of mScarlet, we are confident that a GECI with mScarlet is feasible. To this end, we propose to continue development using a mammalian cell-based screening, instead of screening in bacterial lysates.