bluuebunny/crossref_metadata_2025_split huggingface dataset:
A surface lipoprotein onPasteurella multocidabinds complement factor I to promote immune evasion
Authors: Nguyen Quynh Huong , Lai Chun Heng Royce , Norris Michael J. , Ng Dixon , Shah Megha , Lai Christine Chieh-Lin , Isenman David E. , Moraes Trevor F. 
Published: October 2024

ABSTRACTPasteurella multocidais the leading cause of wound infections in humans following animals’ bites or scratches. This bacterium is also commonly found in the respiratory tract of many mammals and can cause serious diseases resulting in the brutal rapid death of infected animals, especially cattle. To prevent these infections in cattle, a subunit-based vaccine utilizing the surface lipoprotein PmSLP was developed and showed remarkable protection with a single dose administration. Here, we report that PmSLP binds host complement factor I (FI) and facilitates cleavage of complement components C3b and C4b independently of any cofactors (e.g FH, C4BP), thereby allowing the pathogen to evade host defence. Cryo-EM structure of PmSLP bound to FI reveals that PmSLP stimulates FI enzymatic activity by stabilizing the catalytic domain. This is the first time that a bacterial protein has been shown to directly activate FI independent of complement cofactors and target all arms of the complement cascade.
Extending sampling approaches for great crested newt (Triturus cristatus) eDNA monitoring
Authors: Harper Lynsey R. , Harper Kirsten J. , Platts Suzie , Irwin Rebecca , Bennett Michael , Jones Ben , Taylor Oliver , Plant Laura , Eccleshall Danielle , Briscoe Andrew , Gorman Luke , Stanhope Kat , Egeter Bastian 
Published: October 2024

AbstractEnvironmental DNA (eDNA) monitoring has been used for great crested newt (Triturus cristatus, GCN) survey in the UK since the publication of a Defra-funded trial in 2014. Surveys can only be performed during a 76-day survey window (15 April – 30 June), and only if approved methods for collection of 6 x 15 mL subsamples for ethanol precipitation are used. However, filtration may be a more effective and sustainable method of eDNA capture than ethanol precipitation, and detection may be possible outside of the current survey window.We investigated whether the GCN eDNA survey season could be extended and filtration could be used for GCN eDNA capture by reviewing the available evidence and conducting a field study from April to October 2022. Paired water samples for ethanol precipitation and filtration were collected from ponds once a month, resulting in 124 ethanol precipitation kits and 124 filtration kits from 25 ponds. All samples were analysed with the approved quantitative PCR assay for GCN.Our results indicate that GCN can be reliably detected using both eDNA capture methods from April to August, with detection rates decreasing in September and October. GCN eDNA detection was comparable or higher with filtration than ethanol precipitation, thus filtration could be a reliable and more sustainable means for assessing GCN presence.Inclusion of filtration as an accepted eDNA capture method for GCN eDNA surveys would allow more water to be processed for robust and reliable estimates of GCN presence. Extending the GCN eDNA survey season to August would allow more waterbodies to be surveyed and identification of sites that provide important habitat for GCN outside of the breeding season. This would also remove logistical challenges and costs associated with completing GCN surveys and laboratory analysis within 10 weeks, improving performance of surveyors and laboratories as well as quality of results. Furthermore, GCN eDNA surveys could be carried out alongside monitoring for other species, which would enable infrastructure projects to develop more effective mitigation measures as well as reduce time required from surveyors and survey costs.
Fusarium graminearumcopper amine-oxidases redundantly increase virulence by converting tryptamine from hydrolyzed plant defense compounds into auxin
Authors: Svoboda Thomas , Ceranic Asja , Spörhase Pia , Bartholomäus Anika , Wiesenberger Gerlinde , Fruhmann Philipp , Beltran Eduardo , Berthiller Franz , Krska Rudolf , Schuhmacher Rainer , Adam Gerhard 
Published: October 2024

AbstractPlant pathogenic fungi have evolved different strategies to interfere with plant defense mechanisms. The well described fungal plant pathogenFusarium graminearumis not only able to produce trichothecene toxins like deoxynivalenol, but also the plant hormone auxin. Highly elevated levels of auxin and auxin derivatives such as IAA-glucoside or IAA amino-acid conjugates were observed in wheat cultivar Apogee infected withF. graminearum. We report thatF. graminearumis able to cleave tryptamine-derived hydroxycinnamic acid amides, e.g. the defense compound coumaroyl-tryptamine. In this study we investigated copper amine-oxidases, candidate genes for auxin biosynthesis converting tryptamine into the IAA precursor indole-3-acetyldehyde. After consecutive knock outs of all seven copper amine oxidases the resulting septuple knock out strain had strongly reduced ability to produce auxin. Virulence of the septuple mutant was significantly impaired while DON productionin plantawas comparable to the wild type. We conclude thatF. graminearum, often presumed to be a simple nectrotroph, has a biotrophic phase and is able to employ plant defense compounds by converting them into defense suppressing auxin.
Loss of O-specific antigen shapesPseudomonas aeruginosapopulation microbiogeography in murine preclinical pulmonary infection model
Authors: Fraser H. , Moustafa D. A. , Goldberg J. B. , Azimi S. 
Published: October 2024

AbstractChronicPseudomonas aeruginosainfections are the hallmark of late-stage lung disease in individuals with cystic fibrosis. During chronic infectionP. aeruginosabecomes the dominant bacteria in the airway. Within-host adaptation ofP. aeruginosaleads to vast phenotypic and genetic population heterogeneity.In vitrostudies show mutations in lipopolysaccharide (LPS) O-specific antigen changes the aggregate formation inP. aeruginosa, however role of these changes in aggregate assemblyin vivois not understood. Using a synthetic CF sputum media and a preclinical murine infection model we assessed how the PAO1 wildtype and O-specific antigen mutants interact with each other, and ifP. aeruginosapopulation heterogeneity affects the colonization of the murine lungs. Our findings suggest that the presence of variants lacking O-specific antigen does not impact the population fitness and size in bothin vitroandin vivo, however it can influence the aggregate volumein vivo.
Aerial root formation in Oaxacan maize (Zea mays) landraces persists into the adult phase and is minimally affected by soil nitrogen and ambient humidity
Authors: Wilker Jennifer , Venado Rafael E. , Infante Valentina , McLimans Caitlin , Robbins Fletcher , Phillips Courtney , Calderón Claudia Irene , Wallace Jason , Ané Jean-Michel 
Published: October 2024

ABSTRACTMaize (Zea mays) is the most widely produced crop in the world, and conventional production requires significant amounts of synthetic nitrogen fertilizer, which has negative economic and environmental consequences. Maize landraces from Oaxaca, Mexico, can acquire nitrogen from nitrogen-fixing bacteria that live in a mucilage secreted by aerial nodal roots. The development of these nodal roots is a characteristic traditionally associated with the juvenile vegetative stage of maize plants. However, mature Oaxacan landraces develop many more nodes with aerial roots than commercial maize varieties. Our study shows that Oaxacan landraces develop aerial roots during both the juvenile and adult vegetative phases and even during early flowering under greenhouse and field conditions. Surprisingly, the development of these roots was only minimally affected by soil nitrogen and ambient humidity. These findings are an important first step in developing maize varieties that can reduce fertilizer needs in maize production across different environmental conditions.
Expansion, restructuring and characterization of theLegionellaceaefamily
Authors: Gabrielli Marco , Cavallaro Alessio , Hammes Frederik 
Published: October 2024

AbstractLegionellaceaeare a large and widespread family of facultative intracellular bacteria with high clinical relevance. WhileLegionella pneumophila, the most clinically relevant species, is relatively well studied, very limited information is available regarding the other species belonging to this family. Here, we analyzed all publicly-availableLegionellaceaegenomes and metagenome-assembled genomes, nearly doubling the number of recognized species and highlighting the need to restructure the family’s taxonomy to include multiple genera that present distinct clinical relevance. We found that secretion systems and traits linked to host invasion vary significant across genus clusters and species, likely influencing their survival in their environment. While genus clusters presented different metabolic capabilities, species closely related toL. pneumophilawere characterized by a more complete metabolism with fewer auxotrophies. Finally, we showed that while species have distinct environmental distributions, niche overlap increases at higher metabolic similarity. Together, our results shed light on the ecology of these microorganisms, highlight the diversity of traits that can occur in closely related facultative intracellular bacteria, and call for the restructuring of this clade to align with genomic information and clinical relevance to aid the management ofLegionellaceaebacteria.Significance StatementLegionellaceaebacteria are responsible for Legionnaires’ disease, the leading waterborne disease in many industrialized countries. Historically, attention was focused onLegionella pneumophilaand the ecology of other species remained largely unknown and unexplored. However, several water safety regulations cover the entireLegionellagenus, currently the only recognized within this large family, including microorganisms with unknown health relevance. Using a comparative genomics approach and leveraging public genomes and amplicon data, we shed light on the scale, diversity and ecology of this family, finding a surprisingly diversity of the traits linked to host invasion and metabolism, likely driving the species’ environmental distributions. This study proposes to restructure the familyLegionellaceaein multiple genera to align with known clinical associations and predicted phenotypes.
A circuit involving the lncRNA MB3 and the driver genes MYC and OTX2 inhibits apoptosis in Group 3 Medulloblastoma by regulating the TGF-β pathway via HMGN5
Authors: Alessia Grandioso , Paolo Tollis , Romana Pellegrini Francesca , Elisabetta Falvo , Alessandro Palma , Francesco Migliaccio , Alessandro Belvedere , Jessica Rea , Giada Tisci , Annamaria Carissimo , Irene Bozzoni , Daniela Trisciuoglio , Monica Ballarino , Pierpaolo Ceci , Pietro Laneve 
Published: October 2024

ABSTRACTBackgroundGroup 3 (G3) is one of the most common, aggressive and fatal subtypes of the paediatric cerebellar tumour Medulloblastoma (MB), primarily driven by the MYC oncogene. Targeting MYC has long been challenging and this, combined with our incomplete understanding of G3 MB molecular bases, has hindered the development of effective targeted therapies. Long noncoding RNAs (lncRNAs), with their extensive oncogenic roles, cancer-specific expression, and connection to MYC biology, offer opportunities for unravelling this complexity and providing new insights and therapeutic targets.MethodologyUsing genome-wide, molecular and cellular assays, we characterised the activity of the MYC-dependent, anti-apoptotic lncRNAlncMB3in G3 MB cells.ResultsThrough transcriptomic and interactomic analyses, we clarifiedlncMB3function and mode-of-action.LncMB3controls the TGF-β pathway, critically altered in G3 medulloblastomagenesis. This regulation occurs via the direct coding-noncoding RNA interaction betweenlncMB3and the mRNA for the epigenetic factor HMGN5, with both sharing targets in the TGF-β cascade. This axis converges on apoptosis through OTX2, another G3 MB driver gene, and photoreceptor lineage genes. Synergistic effects betweenlncMB3targeting and cisplatin treatment underscores the relevance of this regulatory networkin vitro. Finally, we propose novel ferritin-based nanocarriers as efficient delivery tools for antisense oligonucleotides targetinglncMB3.ConclusionsLncMB3emerges as a central node linking MYC amplification to apoptosis inhibition through a circuit involving RNA-based mechanisms, G3 MB key drivers and underexplored factors. This integrated framework deepens our understanding of G3 MB molecular underpinnings and lay the foundation for translating lncRNA research into potential applications.
Unveiling the Gut Microbiome Network Fingerprint: A Deep Learning Approach to Predict Immunotherapy Response in Melanoma Patients
Authors: Sun Jie , Fan Zhenjiang , Sriram Aditya , Park Hyun Jung 
Published: October 2024

AbstractImmune checkpoint inhibitors (ICI) are critical in cancer therapy, harnessing the immune system to fight tumors. The gut microbiome, a diverse ecosystem of trillions of microorganisms, has emerged as a key influencer of ICI efficacy. However, the specific gut bacteria linked to ICI response in melanoma patients remain unclear, with studies showing inconsistent findings across cohorts. Attributing the lack of consensus to multiple layers of non-linear interactions with host factors and within the microbial community, we developed DeepMicroNET, a novel deep neural network (DNN) model-driven network analysis method to identify and characterize the gut bacteria associated with treatment response. Utilizing data from five cohorts of advanced melanoma patients undergoing ICI therapies, we demonstrate how DeepMicroNET identifies gut bacteria consistently predicting immunotherapy responses (response-associated or RA bacteria). Further, DeepMicroNET revealed that these bacteria are associated with key immune pathways, such as antigen processing and presentation, offering novel insights into the molecular mechanisms that could be targeted to improve therapeutic outcomes. Altogether, by identifying gut bacteria robustly associated with immunotherapy response, DeepMicroNET opens the door to a new era of personalized medicine based on the gut microbiome profile.
Pseudomonas aeruginosasupports the survival ofPrevotella melaninogenicain a cystic fibrosis lung polymicrobial community through metabolic cross-feeding
Authors: El Hafi Bassam , Jean-Pierre Fabrice , O’Toole George A. 
Published: October 2024

AbstractCystic fibrosis (CF) is a multi-organ genetic disorder that affects more than 100,000 individuals worldwide. Chronic respiratory infections are among the hallmark complications associated with CF lung disease, and these infections are often due to polymicrobial communities that colonize the airways of persons with CF (pwCF). Such infections are a significant cause of morbidity and mortality, with studies indicating that pwCF who are co-infected with more than one organism experience more frequent pulmonary exacerbations, leading to a faster decline in lung function. Previous work established anin vitroCF-relevant polymicrobial community model composed ofP. aeruginosa,S. aureus,S. sanguinis, andP. melaninogenica.P. melaninogenicacannot survive in monoculture in this model. In this study, we leverage this model to investigate the interactions betweenP. aeruginosaandP. melaninogenica, allowing us to understand the mechanisms by which the two microbes interact to support the growth ofP. melaninogenicaspecifically in the context of the polymicrobial community. We demonstrate a cross-feeding mechanism wherebyP. melaninogenicametabolizes mucin into short-chain fatty acids that are in turn utilized byP. aeruginosaand converted into metabolites (succinate, acetate) that are cross-fed toP. melaninogenica, supporting the survival of this anaerobe in the CF lung-relevant model.ImportancePolymicrobial interactions impact disease outcomes in pwCF who suffer from chronic respiratory infections. Previous work established a CF-relevant polymicrobial community model that allows experimental probing of these microbial interactions to achieve a better understanding of the factors that govern the mechanisms by which CF lung microbes influence each other. In this study, we investigate the interaction betweenP. aeruginosaandP. melaninogenica, which are two highly prevalent and abundant CF lung microbes. We uncover a cross-feeding mechanism that requires the metabolism of mucin byP. melaninogenicato generate short-chain fatty acids that are cross-fed toP. aeruginosa, and into metabolized into metabolites which are then cross-fed back toP. melaninogenicato support the growth of this anaerobe.
ARhodopseudomonasstrain with a substantially smaller genome retains the core metabolic versatility of its genus
Authors: Oda Yasuhiro , Nelson William C. , Alexander William G. , Nguyen Stella , Egbert Robert G. , Harwood Caroline S. 
Published: October 2024

ABSTRACTRhodopseudomonasare a group of phototrophic microbes with a marked metabolic versatility and flexibility that underpins their potential use in production of value-added products, bioremediation and plant growth promotion. Members of this group have an average genome size of about 5.5 Mb, but two closely related strains have genome sizes of about 4.0 Mb. To identify the types of genes missing in a reduced genome strain, we compared strain DSM127 with otherRhodopseudomonasisolates at the genomic and phenotypic levels. We found that DSM127 can grow as well as other members of theRhodopseudomonasgenus and retains most of their metabolic versatility, but it has many fewer genes associated with high affinity transport of nutrients, iron uptake, nitrogen metabolism and biodegradation of aromatic compounds. This analysis indicates genes that can be deleted in genome reduction campaigns and suggests that DSM127 could be a favorable choice for biotechnology applications usingRhodopseudomonasor as a strain that can be engineered further to reside in a specialized natural environment.IMPORTANCERhodopseudomonasare a cohort of phototrophic bacteria with broad metabolic versatility. Members of this group are present in diverse soil and water environments and some strains are found associated with plants and have plant growth promoting activity. Motivated by the idea that it may be possible to design bacteria with reduced genomes that can survive well only in a specific environment or that may be more metabolically efficient, we comparedRhodopseudomonasstrains with typical genome sizes of about 5.5 Mb to a strain with a reduced genome size of 4.0 Mb. From this we concluded that metabolic versatility is part of the identity of theRhodopseudomonasgroup, but high-affinity transport genes and genes of apparent redundant function can be dispensed with.
Stem and progenitor cell proliferation are independently regulated by cell type-specificcyclinDgenes
Authors: Lush Mark E. , Tsai Ya-Yin , Chen Shiyuan , Münch Daniela , Peloggia Julia , Sandler Jeremy E. , Piotrowski Tatjana 
Published: October 2024

SummaryRegeneration and homeostatic turnover of solid tissues depend on the proliferation of symmetrically dividing adult stem cells, which either remain stem cells or differentiate based on their niche position. Here we demonstrate that in zebrafish lateral line sensory organs, stem and progenitor cell proliferation are independently regulated by twocyclinDgenes. Loss ofccnd2aimpairs stem cell proliferation during development, while loss ofccndxdisrupts hair cell progenitor proliferation but allows normal differentiation. Notably,ccnd2acan functionally replaceccndx, indicating that the respective effects of these Cyclins on proliferation are due to cell type-specific expression. However, even though hair cell progenitors differentiate normally inccndxmutants, they are mispolarized due tohes2and Emx2 downregulation. Thus, regulated proliferation ensures that equal numbers of hair cells are polarized in opposite directions. Our study reveals cell type-specific roles forcyclinDgenes in regulating the different populations of symmetrically dividing cells governing organ development and regeneration, with implications for regenerative medicine and disease.
Cluster Assembly Dynamics Drive Fidelity of Planar Cell Polarity Polarization
Authors: Nissen Silas Boye , Weiner Alexis T. , Suyama Kaye , Bosch Pablo Sanchez , Yu Maiya , Song Song , Gu Yuan , Dunn Alexander R. , Axelrod Jeffrey D. 
Published: October 2024

ABSTRACTIn planar cell polarity (PCP) signaling, distinct molecular subcomplexes segregate to opposite sides of each cell, where they interact across intercellular junctions to form asymmetric clusters. Although proximal-distal asymmetry within PCP clusters is the defining feature of PCP signaling, the mechanism by which this asymmetry develops remains unclear. Here, we developed a method to count the number of monomers of core PCP proteins within individual clusters in live animals and used it to infer the underlying molecular dynamics of cluster assembly and polarization. Measurements over time and space in wild type and in strategically chosen mutants demonstrate that cluster assembly is required for polarization, and together with mathematical modeling provide evidence that clusters become increasingly asymmetric and correctly oriented as they increase in size. We propose that cluster assembly dynamics amplify weak and noisy inputs into a robust cellular output, in this case cell and tissue-level polarization.
Endothelial cell Nrf2 controls neuroinflammation following a systemic insult
Authors: Zou Haoyu , Huang Zhuochun , Leah Tom , He Xin , Dando Owen , Qiu Jing 
Published: October 2024

SummarySystemic inflammation can lead to neuroinflammation with acute consequences such as delirium and long-lasting deleterious effects including cognitive decline and the exacerbation of neurodegenerative disease progression. Here we show that the activation status of the transcription factor Nrf2 in endothelial cells is a critical regulator of this process. We found that peripheral inflammation caused infiltration of macrophages, microglial activation and inflammatory reactive astrogliosis, all of which could be prevented by RTA-404, an activator of the transcription factor Nrf2 and close structural relative of the recently FDA-approved Nrf2 activator RTA-408 (Omaveloxolone). To identify the key cellular mediator(s), we generated an endothelial cell-specific Nrf2 knockout mouse. Strikingly, the effects of RTA-404 on brain endothelial activation and downstream neuroinflammatory events was abolished by endothelial cell-specific Nrf2 deletion. This places endothelial cell Nrf2 as a peripherally accessible therapeutic target to reduce the CNS-adverse consequences of systemic inflammation.