bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coexistence of Virome-Encoded Human Probiotic Genes and Pathogenic Genes in Global Habitats
Authors: Qian Min , Zhu Dong , Yao Ke-yu , Liu Shu-yue , Li Meng-ke , Ye Mao , Zhu Yong-guan 
Published: January 2025

ABSTRACTSome probiotic genes for humans obtained through horizontal gene transfer (HGT) have been screened in viral genomes, yet the occurrence mode, geographic distribution, and functional characteristics of these genes in viruses and the coexistence between pathogenic virulence genes and probiotic genes in the viral genome, remain insufficiently understood and verified. In this study, using IMG/VR v4 database, 4,556 viruses carrying probiotic gene segments have been discovered in eight habitat types (humans, animals, freshwater, marine, other water bodies, soil, and plants), 13 regions of 76 countries around the world. Among them, the 478 viruses carrying probiotic genes that distributed in humans account for the highest proportion among the viruses with predictable hosts. In viruses carrying probiotic genes,BCO1,bioB,COQ2,GPX1,GSTs,GSTT1,GULO,andmenAare not only probiotic genes encoded by viruses, but also auxiliary metabolic genes. Four virulence genes harmful to humans in viral sequences carrying probiotic genes with transcription and expression potential, have been found, indicating that virulence genes encoded by viruses can coexist with probiotic genes. Further metagenome sequencing revealed the consistency between the probiotic gene asd in the bacillus prophage and the corresponding phage auxiliary metabolic genes. This study integrates probiotic gene databases into viral genomics, revealing the compatibility between viral probiotic and virulence genes, and offering new insights for viral applications.IMPORTANCEProbiotic genes acquired by humans through horizontal gene transfer (HGT) have been identified within viral genomes. However, their occurrence, distribution, and functions, along with the coexistence of pathogenic and probiotic genes in viruses, remain poorly understood. This study advocates for the utilization of probiotic gene databases in viral genomes and innovatively elucidates the phenomenon of compatibility between viral probiotic genes and virulence genes, offering fresh perspectives on the diverse applications of viruses. By promoting the application of these databases, the study reveals the compatibility between probiotic and pathogenic genes in viruses, providing novel and insightful implications for the various utilizations of viruses.
Impacts of Habitat Transformation on Amphibian and Reptile Communities in a Heterogeneous Andean Landscape
Authors: Falcón-Espitia Nelson , Ríos-Orjuela Juan Camilo , Perez-Rojas Sebastian , Plazas-Cardona Dennys , Arias-Escobar Alejandra 
Published: January 2025

AbstractThe Andean region of Colombia is recognized for its exceptional biodiversity and high levels of endemism, particularly among amphibians and reptiles. However, this region faces significant challenges due to habitat loss and fragmentation driven by agricultural activities, urbanization, and livestock farming. This study evaluates the effects of habitat alterations on herpetofaunal communities within the Sumapaz province, focusing on three habitat types: secondary Andean forests, coffee plantations, and open areas associated with low-intensity livestock farming. We also compiled a comprehensive inventory of 85 species based on fieldwork conducted (2021-2022) and biodiversity databases, recognizing 35 amphibians and 50 reptiles for the region. We found that forests support the highest richness and diversity of species, while open areas exhibited greater reptile abundance. Crops showed lower biodiversity but demonstrated potential as secondary habitats for certain species. These findings highlight the importance of preserving forested areas and designing mixed-use landscapes to promote biodiversity and maintain ecological functions. This study provides a baseline for future conservation strategies in the Sumapaz region.
Single-Photon Single-Particle Tracking
Authors: Xu Lance W.Q. , Ronceray Nathan , Mitsioni Marianna Fanouria , Radenovic Aleksandra , Pressé Steve 
Published: January 2025

AbstractMultiple biological “particles”, from biomolecules to viral capsids, diffuse with rates exceeding 1µm2/s, introducing blurring so significant when imaged with traditional integrative detectors such as sCMOSs and EMCCDs that one particle may appear as many. While single-photon detector arrays hold promise to strongly mitigate blurring artefacts by allowing for tenfold temporal resolution improvement, tracking from arrays with binary 1-bit output (photon detected or not) falls outside the existing tracking paradigm. For instance, the core of existing tracking algorithms relies on intensity-based information per pixel to achieve single-particle localization. Yet this is not possible with a 1-bit output. Here, we circumvent the localization paradigm and directly analyze single-photon detector array output to leverage the temporal resolution afforded by short single-photon detector array exposures. To achieve this, we propose a computationally feasible strategy to propose particle numbers and associated trajectories consistent with the entire 1-bit per pixel image stack. Our method, single-photon single-particle tracking (SP2T), deals with both hot and cold pixels to which single-photon detector array data interpretation is highly sensitive. We consider multiple examples, including controlled experiments with fluorescent beads following pre-programmed trajectories, where ground truth is partially available, and the diffusion of aerolysin monomers on supported lipid bilayers. These results showcase SP2T as a powerful tool capable of tenfold temporal resolution improvement for advancing the resolution of dynamical events from single-photon detector array architectures.
Exploring vitamin D and its analogues as a possible therapeutic intervention in targeting inflammatory mediators in neurodegenerative disorders like Parkinson’s disease
Authors: Pal Randrita , Das Nilansu , Basu Barnali Ray 
Published: January 2025

AbstractParkinson’s disease characterized by dopaminergic neuronal death has been linked with neuroinflammatory processes which involve self-perpetuating detrimental events leading to prolonged neurodegeneration. Vitamin D has been found to possess neuroprotective and immuno-modulatory effects which might justify elevated inflammation and hypovitaminosis D in PD patients. So, we aimed to find the possible interactions of Vitamin-D and its analogues with inflammatory mediators prevalent in PD to get more insight into Vitamin-D’s role in neuroinflammation by assessing specific interactions between Vitamin-D and its marketed analogues with different inflammatory mediators. Moreover, revealing a possible drug repurposing with Vitamin-D analogues against neuroinflammation and other inflammatory conditions.Molecular docking was conducted with 10 inflammatory markers (p38 MAPK, NF-κB, iNOS, nNOS, COX-2, TNFα, IL6, TNFα, IL1β, CRP) with bio-active form of Vitamin-D (calcitriol) and its analogues. Among the studied ligands, calcitriol, calcipotriol, seocalcitol, paricalcitol and falecalcitriol were found to be potential inhibitors of different inflammatory agents. Specific standard drugs or experimental inhibitors were used to compared the binding affinity between protein and ligand. BBB permeability of the tested ligands also checked as well as neurotoxicity. Most of the ligands were found to be BBB permeable possibly interacting with inflammatory mediators within the brain and were also found to be non-neurotoxic.This study sheds light on VD and its analogues being possible candidates against various inflammatory markers. The findings could further be used as stepping stone for new study on repurposing of these analogues in neuroinflammation and other inflammatory disease conditions.
Improving SBRT by re-wiring immunosuppressive neutrophils in murine pancreatic ductal adenocarcinoma
Authors: Murphy Joseph D. , Hannon Gary , Mills Bradley N. , Hughson Angela L. , Uccello Taylor P. , Gavras Nicholas W. , Ye Jian , Belt Brian A. , Lesch Maggie L. , Eckl Sarah L. , Lord Edith M. , Kim Minsoo , Qiu Haoming , Linehan David C. , Gerber Scott A. 
Published: January 2025

AbstractRadiation is used to treat pancreatic ductal adenocarcinoma (PDAC) in the locally-advanced setting. Stereotactic body radiation therapy (SBRT), in particular, has shown improved outcomes against conventional RT in a number of clinical trials. One key cell type involved in the response to RT are neutrophils. These innate immune cells are the first responders to tissue damage and infiltrate irradiated tumors in high numbers to rectify injury. Neutrophils typically possess an immunosuppressive, wound healing phenotype in this scenario, which allows the tumor to recover and actively suppress immunological efforts to eradicate the disease. Here, we aimed to elucidate the role of neutrophils in a murine model of PDAC treated with SBRT. Mice harboring PDAC tumors were treated with targeted SBRT and neutrophils were determined to be significantly increased in the tissue when compared to unirradiated controls. Additionally, phenotypic analysis determined that these cells were largely immunosuppressive and depletion studies confirmed they played a key role in acquired radioresistance in our model. In order to establish whether these infiltrating cells could be re-wired to contribute to anti-tumor immunity, we utilized a novel combination therapy consisting of SBRT and microspheres containing recombinant IL-12 to attempt to repolarize these cells. Transcriptomic analysis confirmed intratumoral neutrophils underwent considerable changes indicative of an immunostimulatory, anti-tumor phenotype following treatment. Moreover, depleting these cells resulted in a loss of treatment efficacy, suggesting that neutrophil re-wiring was vital for the therapeutic outcome. This study highlights neutrophils as key players in SBRT and IL-12 treatment and confirms they can act as a double-edged sword depending on the treatment employed.
How does urbanization shape shell phenotype, behaviour and parasite prevalence in the snailCornu aspersum?
Authors: Dahirel Maxime , de Tombeur Youna , Gérard Claudia , Ansart Armelle 
Published: January 2025

AbstractUrbanization is a complex and multivariate environmental change inducing major disturbances, e.g. habitat fragmentation/loss, changes in local climate, soil imperviousness, pollution… As slow-moving, ectothermic and humidity-sensitive animals, land snails have to cope with urbanization-induced changes, likely to influence their behaviour, life traits and host-parasite interactions. In this context, we studied how, in the brown garden snailCornu aspersum, shell phenotype (shell size and colour/reflectance), behaviour (food intake, mobility) and metazoan parasite prevalence respond to urbanization. We found that snails from more urbanized sites closer to the urban centre were smaller, whereas urbanization had no detectable effect on shell reflectance, parasite prevalence or behaviour. Larger snails and snails with paler shells were more likely to be infected by trematode metacercariae and sexually-transmitted nematodes (Nemhelix bakeri), respectively. Snails harbouring trematode sporocysts ate typically less, while those infected byN. bakerimoved more slowly. We discuss the decrease of snail size along the urbanization gradient in relation with the Urban Heat Island effect and the potential decrease of resource quality and availability in urban sites. The absence of detectable effects of urbanization on shell reflectance, mobility and prevalence may be due to scale mismatches between how urbanization is measured and how snails experience microhabitats. We propose further experimental and field studies to decipher interactions between urbanization effects, shell phenotype, life-history traits and parasitism.
Langerhans Cells Drive Tfh and B Cell Responses Independent of Canonical Cytokine Signals
Authors: Bouteau Aurélie , Qin Zhen , Zurawski Sandra , Zurawski Gerard , Igyártó Botond Z. 
Published: January 2025

ABSTRACTDendritic cells (DCs) are key regulators of adaptive immunity, guiding T helper (Th) cell differentiation through antigen presentation, co-stimulation, and cytokine production. However, in steady-state conditions, certain DC subsets, such as Langerhans cells (LCs), induce T follicular helper (Tfh) cells and B cell responses without inflammatory stimuli. Using multiple mouse models andin vitrosystems, we investigated the mechanisms underlying steady-state LC-induced adaptive immune responses. We found that LCs drive germinal center Tfh and B cell differentiation and antibody production independently of interleukin-6 (IL-6), type-I interferons, and ICOS ligand (ICOS-L) signaling, which are critical in inflammatory settings. Instead, these responses relied on CD80/CD86-mediated co-stimulation. Our findings challenge the conventional three-signal paradigm by demonstrating that cytokine signaling is dispensable for LC-mediated Tfh and B cell responses in steady-state. These insights provide a framework for understanding homeostatic immunity and the immune system’s role in maintaining tolerance or developing autoimmunity under non-inflammatory conditions.SUMMARY STATEMENTLangerhans cells (LCs) drive germinal center Tfh and B cell responses in steady-state conditions independently of IL-6, type-I interferons, and ICOS ligand, challenging the established cytokine-centric model of T cell differentiation.
MISO: Microfluidic protein isolation enables single particle cryo-EM structure determination from a single cell colony
Authors: Eluru Gangadhar , De Gieter Steven , Schenck Stephan , Stroobants Annelore , Shrestha Binesh , Erbel Paul , Brunner Janine D. , Efremov Rouslan G. 
Published: January 2025

AbstractSingle particle cryo-EM enables reconstructing near-atomic or even atomic resolution 3D maps of proteins by visualizing thousands to a few million purified protein particles embedded in nanometer- thick vitreous ice. This corresponds to picograms of purified protein, which can potentially be isolated from a few thousand cells. Hence, cryo-EM holds the potential of one of the most sensitive analytical methods that deliver a high-resolution protein structure as a readout. In practice, more than a million times more starting biological material is required to prepare cryo-EM grids. To close the gap, we developed a micro isolation (MISO) method that combines microfluidics-based protein purification with cryo-EM grid preparation. We validated the method on soluble bacterial and eukaryotic membrane proteins. We showed that MISO enables protein structure determination starting from below one microgram of a target protein and going from cells to cryo-EM grids within a few hours. This scales down the purification by a factor of a few hundred to a few thousand and opens possibilities for the structural characterization of hitherto inaccessible proteins.
CryoNeRF: reconstruction of homogeneous and heterogeneous cryo-EM structures using neural radiance field
Authors: Qu Huaizhi , Wang Xiao , Zhang Yuanyuan , Wang Sheng , Noble William Stafford , Chen Tianlong 
Published: January 2025

AbstractCryogenic electron microscopy (cryo-EM) has become a widely used technique for determining the 3D structures of proteins. However, cryo-EM datasets often exhibit heterogeneity, with protein particle images from multiple conformations or compositional states. Here we proposeCryoNeRF, a novel neural radiance fields (NeRF)-based cryo-EM reconstruction framework operating directly in Euclidean 3D space. CryoNeRF introduces a multi-resolution hash encoding and heterogeneity-aware cryo-EM encoder to model cryo-EM heterogenity. Extensive experiments demonstrate the stability and superior performance of CryoNeRF in both homogeneous and heterogeneous settings. On homogeneous datasets, CryoNeRF achieves 15.8% improvement over previous state-of-the-art methods. On both simulated and experimental heterogeneous datasets, CryoNeRF demonstrates exceptional capability in handling both conformational and compositional variations, which is consistent with previous experimental discoveries. Notably, CryoNeRF successfully distinguishes assembly states that even only account for 2% particles of the dataset in cases of compositional heterogeneity.
Antibiotic ResistantE. Coliare Common in Waller Creek, an Urban Waterway Chronically Contaminated with Fecal Bacteria
Authors: Olivera Perez Lena L. , Reichler Stuart 
Published: January 2025

AbstractThe emergence of antibiotic-resistant bacteria has created a significant threat to global health. Some strains ofEscherichia coli(E. coli), a common bacteria with both commensal and pathogenic strains, can be resistant to common antibiotics. This study investigates the prevalence ofE. coliresistance to ampicillin, erythromycin, and ciprofloxacin in Waller Creek, an urban waterway in Austin, Texas with chronically high levels of fecal bacteria. Approximately 134 samples were collected from three different sites along Waller Creek and spiked with varying antibiotic concentrations.E. coliresistance to ampicillin and erythromycin was found to be up to 26.92% and 48.37% respectively, while resistance to ciprofloxacin was much lower ranging between 0%-2%. The highest levels of resistance were associated with dense urbanization, high levels of homelessness, and after heavy precipitation. These findings indicate the need for regular monitoring of antibiotic concentrations and antibiotic resistant fecal bacteria within urban waterways. This data is needed to identify potential human health risks and understand key factors that contribute to the quantity of antibiotic-resistant pathogens.
TrueSpot: A robust automated tool for quantifying signal puncta in fluorescent imaging
Authors: Hospelhorn Blythe G. , Kesler Benjamin K. , Jashnsaz Hossein , Neuert Gregor 
Published: January 2025

AbstractCharacterizing the movement of biomolecules in single cells quantitatively is essential to understanding fundamental biological mechanisms. RNA fluorescent in situ hybridization (RNA-FISH) is a technique for visualizing RNA in fixed cells using fluorescent probes. Automated processing of the resulting images is essential for large datasets. Here we demonstrate that our RNA-FISH image processing tool, TrueSpot, is useful for automatically detecting the locations of RNA at single molecule resolution. TrueSpot also performs well on images with immunofluorescent (IF) and GFP tagged clustered protein targets. Additionally, we show that our 3D spot detection approach substantially outperforms current 2D spot detection algorithms.
Polysialylation is a general feature of immune activation
Authors: Makhsous Sogand , Hunter Carmanah , van Eeden Charmaine , Osman Mohammed , Willis Lisa 
Published: January 2025

AbstractSialic acids are critical regulators of immune responses and the sialic acid-Siglec axis has receive much attention recently for it role as a new immune checkpoint. While α2,3- and α2,6-linked sialosides have been well studied, much less is known about the α2,8-linked polysialic acid (polySia), especially in the adaptive immune system. We demonstrate here that polySia is actually found in all major classes of circulating immune cells, including B and T cells, where it is strongly associated with prior antigen exposure. Cell surface expression of polySia could be observed within 24 h of activation of naïve T cells but did not correlate with expression of the immune-specific polysialyltransferase ST8Sia4. Finally, we assessed the effects of smoking on polySia levels, and noted substantial increased levels of polySia, particularly on effector T cells and preferentially in males.Significance StatementThe immune system is central to human health and holds the key to treating many chronic diseases. We show for the first time that the immunomodulatory glycan polysialic acid is widespread in the human immune system and associated with immune cell activation. Moreover, sex-dependent increases in polysialic acid could be observed on key populations of immune effector cells in smokers. This study offers insight into how glycans might contribute to sex differences in development and progression of chronic diseases.
Light-induced conformational switching and magnetic sensitivity of Drosophila cryptochrome
Authors: Chandler Shane A. , Gehrckens Angela S. , Shah Laila M. N. , Buckton Katherine E. , Cao Guodong , Sen Navoneel , Zollitsch Tilo , Rodriguez Ryan , Solov’yov Ilia A. , Schleicher Erik , Weber Stefan , Hore Peter J. , Timmel Christiane R. , Mackenzie Stuart R. , Benesch Justin L.P. 
Published: January 2025

SUMMARYCryptochromes are flavoproteins with a number of established and proposed biological functions based on their sensitivity to light. Amongst the latter is the possibility that cryptochromes mediate the geomagnetic compass sense used by migratory birds as a navigational cue. This hypothesis rests on a magnetically sensitive photochemical reaction of the flavin chromophore in which a series of electron transfers within the protein scaffold ultimately generates a signal propagated within the central nervous system of the animal. Although there is a good understanding of the photochemistry and the electron transfer pathway, the protein-mediated mechanisms of signal transduction are still unclear. Here we have examined the response ofDrosophila melanogastercryptochrome –DmCRY, an archetypal cryptochrome – to photochemical activation by means of molecular dynamics simulations, hydrogen-deuterium exchange mass spectrometry, and cavity ring-down spectroscopy. We were able to measure the dynamics ofDmCRY at near-residue level resolution, revealing a reversible, long-lived, blue-light induced conformational change in the C-terminal tail of the protein. This putative signalling state was validated using different illumination conditions, and by examiningDmCRY variants in which the electron transfer chain was disrupted by point mutation. Our results show how the photochemical behaviour of the flavin chromophore generates a state ofDmCRY that may act as a key primer for modulating downstream interactions.
A systematic screen for genetic factors underpinning transposon defense systems across the fungal kingdom
Authors: Badet Thomas , Croll Daniel 
Published: January 2025

AbstractFungal genome sizes exhibit more than a 100-fold variation, largely driven by the expansion of repetitive sequences such as transposable elements (TEs). Genomic defenses have evolved to counteract TE proliferation through silencing mechanisms operating at the epigenetic or transcript level. In fungi, repeat-induced point mutation (RIP) targets TEs by recognizing repetitive sequences and inducing mutagenesis. However, the prevalence of RIP across the fungal kingdom and the fidelity of the canonical C-to-T mutation signatures remain unclear. In this study, we address these gaps by tracking shifts in genome architecture across the fungal kingdom. We show that the loss of RIP components is associated with an 80% (∼30 Mb) increase in genome size in ascomycetes (class of Leotiomycetes). To track the impact of genome defenses, we designed a quantitative screen for RIP-like mutation signatures. The phylum of ascomycetes was unique in showing enrichment in mutation signatures in non-coding and repetitive sequences, consistent with a phylogenetically restricted occurrence of RIP-like genome defense systems. Then, we gene functions associated in a phylogenetic context with RIP-like mutation signatures. We identified a zinc-finger protein as the strongest candidate underpinning a novel mechanism of genome defenses. Our findings reveal the multifaceted drivers of genome defense systems and their close ties to genome size evolution in fungi, highlighting how proximate molecular mechanisms can shape genome evolution on deep phylogenetic scales.