bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lydicamycins Induce Morphological Differentiation in Actinobacterial Interactions
Authors: Jarmusch Scott A. , Schostag Morten D. , Yang Zhijie , Wang Jinglin , Anderson Aaron J.C. , Weber Tilmann , Ding Ling 
Published: July 2024

Streptomycesare major players in soil microbiomes, however, interactions involvingStreptomycesand other actinobacteria are rarely described. The complex developmental cycle of actinobacteria necessitates a multi-omics approach to unravel the web of information. This study resulted from the observation of induced morphogenesis between two environmental isolates from the same site,Kitasatosporasp. P9-2B1 andStreptomycessp. P9-2B2. When co-cultivated on potato dextrose agar (PDA), P9-2B2 induced a wave-like sporulation in strain P9-2B1. Using massspectrometry imaging, we revealed that a suite of lydicamycins were present in this induced sporulation zone. Lydicamycin deficient mutants were generated using CRISPR Base-Editing and the inducible sporulation ceased, confirming their role in triggering morphological differentiation. In agar diffusion assays, pure lydicamycin was inhibitory when added concurrently with bacterial inoculation and induced sporulation with delayed addition. Subsequent testing of additional environmental isolates resulted in the same inducible sporulation wave phenomenon, includingStreptomyces coelicolorM145 and M1146. Using transcriptomics, we observed the differential expression of genes related to early aerial mycelium development four days into cocultivation and the transitional genes responsible for development of spores on day 9. Along with these differentially expressed genes, we also observed numerous overall stress responses, specifically cell envelope stress responses. These findings uncovered actinobacteria interactions mediated by lydicamycins, pointing to a potential role of certain groups of bioactive metabolites in nature.ImportanceShifting away from an antibiotic discovery mindset, uncovering the chemical ecology of secondary metabolites is key to maximizing their biotechnological application. The reduced complexity of dual cultures allows for in depth analysis and investigation of these interactions via multi-omics provides orthogonal data leading to more robust conclusions. This study provides insight into the role of lydicamycins in dual cultures with other actinobacteria and provides an integral roadmap for future chemical ecology work between microorganisms, especially through the use of mass spectrometry imaging.
Castanet: a pipeline for rapid analysis of targeted multi-pathogen genomic data
Authors: Mayne Richard , Secret Shannah , Geoghegan Cyndi , Trebes Amy , Kean Kai , Reid Kaitlin , Lin Gu-Lung , Ansari M. Azim , de Cesare Mariateresa , Bonsall David , Elliott Ivo , Piazza Paolo , Brown Anthony , Bray James , Knight Julian C. , Harvala Heli , Breuer Judith , Simmonds Peter , Bowden Rory J. , Golubchik Tanya 
Published: July 2024

AbstractMotivationTarget enrichment strategies generate genomic data from multiple pathogens in a single process, greatly improving sensitivity over metagenomic sequencing and enabling cost-effective, high throughput surveillance and clinical applications. However, uptake by research and clinical laboratories is constrained by an absence of computational tools that are specifically designed for the analysis of multi-pathogen enrichment sequence data. Here we present the Castanet pipeline: an analysis pipeline for end-to-end processing and consensus sequence generation for use with multi-pathogen enrichment sequencing data. Castanet is designed to work with short-read data produced by existing targeted enrichment strategies, but can be readily deployed on any BAM file generated by another methodology. It is packaged with usability features, including graphical interface and installer script.ResultsIn addition to genome reconstruction, Castanet reports method-specific metrics that enable quantification of capture efficiency, estimation of pathogen load, differentiation of low-level positives from contamination, and assessment of sequencing quality. Castanet can be used as a traditional end-to-end pipeline for consensus generation, but its strength lies in the ability to process a flexible, pre-defined set of pathogens of interest directly from multi-pathogen enrichment experiments. In our tests, Castanet consensus sequences were accurate reconstructions of reference sequences, including in instances where multiple strains of the same pathogen were present. Castanet performs effectively on standard laptop computers and can process the entire output of a 96-sample enrichment sequencing run (50M reads) using a single batch process command, in<2 h.Availability and ImplementationSource code freely available under GPL-3 license athttps://github.com/MultipathogenGenomics/castanet, implemented in Python 3.10 and supported in Ubuntu Linux 22.04 and other Bash-like environments. The data for this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB77004.
IGF2BP3 promotes the progression of gastric cancer by activating cGMP-PKG signaling pathway via targeting FBXO32
Authors: Si Yi , Tian Bo , Zhang Rui , Xuan Mingda , Liu Kunyi , Jiao Jiao , Han Shuangshuang , Li Hongfei , Hu Yanhong , Zhao Hongyan , He Wenjing , Wang Jia , Liu Ting , Yu Weifang 
Published: July 2024

AbstractN6-methyladenosine (m6A) represents the most prevalent chemical modification on eukaryotic mRNA, with an accumulating body of literature indicating its pivotal significance in the pathogenesis of human cancers. Nevertheless, the precise molecular interplay between the m6A reader protein IGF2BP3 and gastric cancer remains to be thoroughly delineated. Our study uncovered that the expression of IGF2BP3 in gastric cancer tissues is markedly elevated in comparison to adjacent normal tissues, and this upregulation is tightly correlated with the incidence of lymph node metastasis, more advanced TNM stages, and deeper invasion depth of tumor in patients.In vitroexperiments demonstrated that IGF2BP3 potentiates the proliferative, migratory, and invasive capacities of gastric cancer cells, while concurrently inhibiting apoptosis and augmenting the intracellular levels of aerobic glycolysis.In vivoexperiments revealed that IGF2BP3 contributes to the growth of gastric cancer. Mechanistically, IGF2BP3 can increase the expression of FBXO32 protein by recognizing and binding to the m6A binding site on FBXO32 mRNA and further activate the downstream cGMP-PKG signaling pathway, thereby modulating various biological functions of gastric cancer cells and ultimately promoting the progression of gastric cancer. In summary, our findings suggest that IGF2BP3 upregulates the expression of FBXO32 protein in an m6A dependent manner and subsequently activates the cGMP-PKG signaling pathway, ultimately leading to the onset and progression of gastric cancer. Consequently, the targeting of the IGF2BP3/FBXO32/cGMP-PKG axis emerges as a promising therapeutic modality for the treatment of gastric cancer.
Unravelling complex hybrid and polyploid evolutionary relationships using phylogenetic placement of paralogs from target enrichment data
Authors: Walden Nora , Kiefer Christiane , Koch Marcus A. 
Published: July 2024

AbstractPhylogenomic datasets comprising hundreds of genes have become the standard for plant systematics and phylogenetics. However, large scale phylogenomic studies often exclude polyploids and hybrids due to the challenges in assessing paralog status of targeted loci and incorporating them into tree reconstruction methods. Using a target enrichment dataset of 1081 genes from 452 samples from the Brassicaceae tribe Arabideae, including many hybrid and high ploidy taxa, we developed a novel approach to disentangle the evolutionary history of this phylogenetically and taxonomically challenging clade. Our approach extends beyond commonly used gene tree-species tree reconciliation techniques by using phylogenetic placement, a method adopted from metagenomics, of paralogous sequences into a diploid tree. We call this approach Paralog PhyloGenomics (PPG), and show how it allows for the simultaneous assessment of the origins of ancient and recent hybrids and autopolyploids, and the detection of nested polyploidization events. Additionally, we demonstrate how synonymous substitution rates provide further evidence for the mode of polyploidization, specifically to distinguish between allo- and autopolyploidization, and to identify hybridization events involving a ghost lineage. Our approach will be a valuable addition to phylogenomic methods available for the study of polyploids.
Linking selection to demography in experimental evolution of active death in a unicellular organism
Authors: Zeballos Nathalie , Rieu Oceane , Fereol Stanislas , Leung Christelle , Chevin Luis-Miguel 
Published: July 2024

AbstractDeciphering how natural selection emerges from demographic differences among genotypes, and reciprocally how evolution affects population dynamics, is key to understanding population responses to environmental stress. This is especially true in non-trivial ecological scenarios, such as programmed cell death (PCD) in unicellular organisms, which can lead to massive population decline in response to stress. To understand how selection may operate on this trait, we exposed monocultures and mixtures of two closely related strains of the microalgaDunalliela salina, one of which induces PCD, to multiple cycles of hyper-osmotic shocks, and tracked demography and selection throughout. Population dynamics were consistent between mixtures and monocultures, suggesting that selection on PCD does not involve strong ecological interactions. The PCD-inducing strain was maintained throughout the experiment despite an initial decline, by a combination of fast population rebound following each decline, and density-dependent competition dynamics near the stationary phase that were independent of these initial population fluctuations. As result of PCD maintenance, population decline in response to environmental stress was not counter-selected in our experiment, but persisted over 13 cycles of salinity. Our results highlight how analysing the demographic underpinnings of fitness and competition can shed light on the mechanisms underlying selection and eco-evolutionary dynamics.
GenomeDelta: detecting recent transposable element invasions without repeat library
Authors: Pianezza Riccardo , Haider Anna , Kofler Robert 
Published: July 2024

AbstractTo evade repression by the host defense, transposable elements (TEs) are occasionally horizontally transferred (HT) to naive species. TE invasions triggered by HT may be much more abundant than previously thought. For example, previous studies inDrosophila melanogasterfound 11 TE invasions over 200 the past years. A major limitation of current approaches for detecting recent invasions is the necessity for a repeat-library, which is notoriously difficult to generate. To address this, we developed GenomeDelta, a novel approach for identifying sample-specific sequences, such as recently invading TEs, without prior knowledge of the sequence. It can thus be used with model and non-model organisms. As input, GenomeDelta requires a long-read assembly and short-read data. It will find sequences in the assembly that are not represented in the short read data. Beyond identifying recent TE invasions, GenomeDelta can detect sequences with spatially heterogeneous distributions, recent insertions of viral elements and recent lateral gene transfers. We thoroughly validated GenomeDelta with simulated and real data from extant and historical specimens. Finally, we demonstrate that GenomeDelta can reveal novel biological insights: we discovered the three most recent TE invasions inDrosophila melanogasterand a novel TE with a geographically heterogeneous distribution inZymoseptoria tritici.
EstroGene2.0: A multi-omic database of response to estrogens, ER-modulators, and resistance to endocrine therapies in breast cancer
Authors: Li Zheqi , Chen Fangyuan , Chen Li , Liu Jiebin , Tseng Danielle , Hadi Fazal , Omarjee Soleilmane , Kishore Kamal , Kent Joshua , Kirkpatrick Joanna , D’Santos Clive , Lawson Mandy , Gertz Jason , Sikora Matthew J. , McDonnell Donald P. , Carroll Jason S. , Polyak Kornelia , Oesterreich Steffi , Lee Adrian V. 
Published: July 2024

AbstractEndocrine therapies targeting the estrogen receptor (ER/ESR1) are the cornerstone to treat ER-positive breast cancers patients, but resistance often limits their effectiveness. Understanding the molecular mechanisms is thus key to optimize the existing drugs and to develop new ER-modulators. Notable progress has been made although the fragmented way data is reported has reduced their potential impact. Here, we introduce EstroGene2.0, an expanded database of its precursor 1.0 version. EstroGene2.0 focusses on response and resistance to endocrine therapies in breast cancer models. Incorporating multi-omic profiling of 361 experiments from 212 studies across 28 cell lines, a user-friendly browser offers comprehensive data visualization and metadata mining capabilities (https://estrogeneii.web.app/). Taking advantage of the harmonized data collection, our follow-up meta-analysis revealed substantial diversity in response to different classes of ER-modulators including SERMs, SERDs, SERCA and LDD/PROTAC. Notably, endocrine resistant models exhibit a spectrum of transcriptomic alterations including a contra-directional shift in ER and interferon signaling, which is recapitulated clinically. Furthermore, dissecting multipleESR1-mutant cell models revealed the different clinical relevance of genome-edited versus ectopic overexpression model engineering and identified high-confidence mutant-ER targets, such asNPY1R.These examples demonstrate how EstroGene2.0 helps investigate breast cancer’s response to endocrine therapies and explore resistance mechanisms.
The coevolution of learning schedules and teaching enhances cumulative knowledge and drives a teacher-innovator syndrome
Authors: Maisonneuve Ludovic , Lehmann Laurent , Mullon Charles 
Published: July 2024

AbstractNatural selection shapes how individuals learn and acquire knowledge from their environment. Under the right conditions, this can lead to the evolution of learning schedules—how individuals allocate resources to acquire knowledge throughout their lifespan—that promote the accumulation of knowledge across generations (“cumulative knowledge” or “cumulative culture”). In spite of having been observed across multiple taxa, the role of parental teaching in this evolutionary process remains understudied. Using mathematical modelling, we show that learning schedules and parental teaching coevolve, resulting in greater time spent learning individually and innovating, as well as greater inter-generational transfer of knowledge from parent to offspring. These outcomes together enhance cumulative knowledge. Our analyses further reveal that within populations, selection typically favours an association between teaching and individual learning whereby some individuals innovate and teach within the family (“knowledge producers” with extensive knowledge), while others teach less and learn socially outside of the family (“knowledge scroungers” with less knowledge). Overall, our findings indicate that the coevolution of learning schedules and teaching promotes knowledge accumulation within and between generations, and favours diversity within and between populations in knowledge acquisition, possession and transmission.
Active surveillance for influenza A virus in swine reveals within-farm reassortment and cocirculation of distinct subtypes and genetic clades
Authors: Thomas Megan N. , Janzen Garrett M. , Markin Alexey , Sharma Aditi , Hewitt Kelly , Li Ganwu , Baker Amy L. , Gauger Phillip C. , Anderson Tavis K. 
Published: July 2024

AbstractInfluenza A virus (IAV) is one of the three most frequently detected respiratory pathogens in swine. A passive IAV in swine surveillance system in the United States (U.S.) provides aggregated national metrics to quantify spatial and temporal changes in genetic diversity.However, swine production is not homogenous: production systems vary in size and management strategies that affect the transmission and evolution of IAV. To assess the impact of fine-scale variation in swine production on IAV transmission, we conducted active surveillance on sow farms and linked nurseries from 4 U.S. production systems for up to 14 monthly collections. From IAV-positive samples, we obtained 85 complete HA sequences, and of these, we successfully assembled 62 whole genomes with associated epidemiological information. To infer transmission and evolution, we conducted Bayesian phylodynamic analyses and detected six genetic clades from four HA lineages: the H1 1A classical swine, the H1 1B human-seasonal, and the H3 2010.1 and 1990.4 lineages. The 1B and H3 1990.4 strains showed evidence of transmission from sow farm to nursery. In contrast, 1A and H3 2010.1 viruses were detected in nurseries without detection in a linked sow farm. We also detected seven separate human-to- swine transmission events in the H1N1 pandemic clade (1A.3.3.2) in sow and nursery sites. Our data demonstrated that nursery sites were infected with IAV that was both linked and unlinked to the sow farm. These data suggest that control efforts may be impacted by subclinical IAV transmission in the breeding herd, the mixing of sow farm sources at the nursery, regional spread of new strains, and human-to-swine transmission. Regular surveillance activities within production systems provide the ability to match vaccine components to circulating diversity, thereby minimizing the opportunity for novel reassorted viruses to emerge and impact animal health.
Atf4 protects islet β-cell identity and function under acute glucose-induced stress but promotes β-cell failure in the presence of free fatty acid
Authors: Yagan Mahircan , Najam Sadia , Hu Ruiying , Wang Yu , Dadi Prasanna , Xu Yanwen , Simmons Alan J. , Stein Roland , Adams Christopher M. , Jacobson David A. , Lau Ken , Liu Qi , Gu Guoqiang 
Published: July 2024

AbstractGlucolipotoxicity, caused by combined hyperglycemia and hyperlipidemia, results in β-cell failure and type 2 diabetes (T2D) via cellular stress-related mechanisms. Activating transcription factor 4 (Atf4) is an essential effector of stress response. We show here thatAtf4expression in β-cells is dispensable for glucose homeostasis in young mice, but it is required for β-cell function during aging and under obesity-related metabolic stress. Henceforth, agedAtf4-deficient β-cells display compromised secretory function under acute hyperglycemia. In contrast, they are resistant to acute free fatty acid-induced loss-of identity and dysfunction. At molecular level,Atf4-deficient β-cells down-regulate genes involved in protein translation, reducing β-cell identity gene products under high glucose. They also upregulate several genes involved in lipid metabolism or signaling, likely contributing to their resistance to free fatty acid-induced dysfunction. These results suggest thatAtf4activation is required for β-cell identity and function under high glucose, but this paradoxically induces β-cell failure in the presence of high levels of free fatty acids. Different branches of Atf4 activity could be manipulated for protecting β-cells from metabolic stress-induced failure.HighlightsAtf4 is dispensable in β-cells in young miceAtf4 protects β-cells under high glucoseAtf4 exacerbate fatty acid-induced β-cell defectsAtf4 activates translation but depresses lipid-metabolism
Muskelin acts as a substrate receptor of the highly regulatedDrosophilaCTLH E3 ligase during the maternal-to-zygotic transition
Authors: Briney Chloe A. , Henriksen Jesslyn C. , Lin Chenwei , Jones Lisa A. , Benner Leif , Rains Addison B. , Gutierrez Roxana , Gafken Philip R. , Rissland Olivia S. 
Published: July 2024

ABSTRACTThe maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that inDrosophilathe deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch (TRAL) are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies. In particular,Drosophilalacks an identifiable substrate adaptor, and the mechanisms restricting degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental specificity of the CTLH complex is mediated by multi-pronged regulation, including transcriptional control by the transcription factor OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate acts as a substrate adaptor for theDrosophilaCTLH complex. Although conserved, Muskelin has structural roles in other species, suggesting a surprising functional plasticity. Finally, we find that Muskelin has few targets beyond the three known RNA binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, seemingly with the goal of regulating three important RNA binding proteins.
Organoid Models Derived from Primary Tumors and Patient-Derive Xenograft Tumors Reflect Platinum Sensitivity of Ovarian Cancer Patients
Authors: Nikeghbal Parisa , Burke Danielle , Steinkamp Mara P. 
Published: July 2024

AbstractOvarian cancer (OC) remains the deadliest gynecological cancer, primarily due to late stage diagnosis and high rates of chemotherapy resistance and recurrence. Lack of representative preclinical models exacerbates the challenges of discovering effective therapies to treat platinum-resistant OC. Patient-derived xenograft (PDX) models maintain the genetic characteristics of the original tumor, but require considerable development time and have limited screening capabilities. Organoid models mimic the tumor’s 3D structure and preserve intra-tumoral heterogeneity, so are ideal for drug screening. The purpose of this study was to determine if PDX-derived organoids (PDXOs) can reflect patient responses to chemotherapy similar to organoids derived from primary patient tumors (PDOs). In drug response assays, PDXOs and PDOs demonstrated similar sensitivity to standard chemotherapy. Furthermore, both PDXOs and PDOs reliably reflected patient response based on the clinical designation of platinum sensitivity. Seven out of eight models derived from six platinum-sensitive cases showed a significant reduction in cell viability when treated with carboplatin, paclitaxel, or the combination therapy. Six of seven organoid models derived from four platinum-resistant or refractory patients demonstrated little to no reduction in cell viability with carboplatin or combination treatment. In these platinum-resistant models, response to single agent paclitaxel was mixed, suggesting that organoid models could predict response to second-line paclitaxel. This study demonstrates that PDXOs can effectively mirror patient responses to chemotherapy, underscoring their potential as valuable, renewable models for screening novel therapies and developing personalized treatment strategies in OC.