bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary fingerprints of EMT in pancreatic cancers
Authors: Perelli Luigi , Zhang Li , Mangiameli Sarah , Russell Andrew J. C. , Giannese Francesca , Peng Fuduan , Carbone Federica , Le Courtney , Khan Hania , Citron Francesca , Soeung Melinda , Lam Truong Nguyen Anh , Lundgren Sebastian , Zhu Cihui , Catania Desiree , Feng Ningping , Gurreri Enrico , Sgambato Alessandro , Tortora Giampaolo , Draetta Giulio F. , Tonon Giovanni , Futreal Andrew , Giuliani Virginia , Carugo Alessandro , Viale Andrea , Heffernan Timothy P. , Wang Linghua , Cittaro Davide , Chen Fei , Genovese Giannicola 
Published: September 2023

AbstractMesenchymal plasticity has been extensively described in advanced and metastatic epithelial cancers; however, its functional role in malignant progression, metastatic dissemination and therapy response is controversial. More importantly, the role of epithelial mesenchymal transition (EMT) and cell plasticity in tumor heterogeneity, clonal selection and clonal evolution is poorly understood. Functionally, our work clarifies the contribution of EMT to malignant progression and metastasis in pancreatic cancer. We leveragedad hocsomatic mosaic genome engineering, lineage tracing and ablation technologies and dynamic genetic reporters to trace and ablate tumor-specific lineages along the phenotypic spectrum of epithelial to mesenchymal plasticity. The experimental evidences clarify the essential contribution of mesenchymal lineages to pancreatic cancer evolution and metastatic dissemination. Spatial genomic analysis combined with single cell transcriptomic and epigenomic profiling of epithelial and mesenchymal lineages reveals that EMT promotes with the emergence of chromosomal instability (CIN). Specifically tumor lineages with mesenchymal features display highly conserved patterns of genomic evolution including complex structural genomic rearrangements and chromotriptic events. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross species analysis of pancreatic and other human epithelial cancers. Mechanistically, we discovered that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, which in turn results in delayed mitosis and catastrophic cell division. Therefore, EMT favors the emergence of high-fitness tumor cells, strongly supporting the concept of a cell-state, lineage-restricted patterns of evolution, where cancer cell sub-clonal speciation is propagated to progenies only through restricted functional compartments. Restraining those evolutionary routes through genetic ablation of clones capable of mesenchymal plasticity and extinction of the derived lineages completely abrogates the malignant potential of one of the most aggressive form of human cancer.
Determining the antiviral mechanism of MARCH2
Authors: Umthong Supawadee , Timilsina Uddhav , D’Angelo Mary , Stavrou Spyridon 
Published: September 2023

AbstractMembrane-associated RING-CH (MARCH) 2 protein is a member of the MARCH protein family of RING-CH finger E3 ubiquitin ligases that have important functions in regulating the levels of proteins found on the cell surface. MARCH1, 2 and 8 inhibit HIV-1 infection by preventing the incorporation of the envelope glycoproteins in nascent virions. However, a better understanding on the mechanism utilized by MARCH proteins to restrict HIV-1 is needed. In this report, we identify an amino acid in human MARCH2, that is absent in mouse MARCH2, critical for its antiretroviral function. Moreover, we map the domains of human MARCH2 critical for restricting as well as binding to the HIV-1 envelope glycoproteins. Our findings reveal important new aspects of the antiviral mechanism utilized by human MARCH2 to restrict HIV-1 that have potential implications to all MARCH proteins with antiviral functions.
CRONOSOJA: a daily time-step hierarchical model predicting soybean development across maturity groups in the Southern Cone
Authors: Severini Alan D. , Álvarez-Prado Santiago , Otegui María E. , Kavanová Monika , Vega Claudia R. C. , Zuil Sebastián , Ceretta Sergio , Acreche Martín , Amarilla Fidencia , Cicchino Mariano , Fernández-Long María E. , Crespo Aníbal , Serrago Román , Miralles Daniel J. 
Published: September 2023

AbstractAccurate prediction of phenology is the most critical aspect for the development of models aimed at estimating seed yield, particularly in species that exhibit variable sensitivity to environmental factors throughout the cycle and among genotypes. With this purpose, we evaluated the phenology of 34 soybean varieties in 43 field experiments located in Argentina, Uruguay, and Paraguay. Experiments covered a broad range of maturity groups (2.2-6.8), sowing dates (from spring to summer), and latitude range (24.9-35.6 °S), thus ensuring a wide range of thermo-photoperiodic conditions during the growing season. Based on the observed data, daily time-step models were developed and tested, first for each genotype, and then across maturity groups. We identified base temperatures specific for different developmental stages and an extra parameter for calculating the photoperiod effect after the R1 stage (flowering). Also, an optimum photoperiod length for each maturity group was found. Model selection showed that the determinants of phenology across maturity groups were mainly affecting the duration of vegetative and early reproductive stages. Even so, early phases of development were better predicted than later ones, particularly in locations with cool growing seasons, where the model tended to overestimate their duration. Overall, we developed a soybean phenology model that, owing to its process-based nature, is able to simulate phenology well across widespread locations and sowing dates yet, because of its simplicity, can be adopted by a wide audience. The final model was made available athttp://cronosoja.agro.uba.ar.
Structural and Functional Disparities within the Human Gut Virome in terms of Genome Topology and Representative Genome Selection
Authors: Veldsman Werner P , Yang Chao , Zhang Zhenmiao , Huang Yufen , Zhang Lu 
Published: September 2023

ABSTRACTCircularity confers protection to viral genomes where linearity falls short, thereby fulfilling the form follows function aphorism. Yet, a shift away from morphology-based classification towards molecular and ecological classification of viruses is currently underway within the field of virology. Recent years have seen drastic changes in the ICTV operational definitions of viruses, particularly for those tailed phages that inhabit the human gut. After the abolition of the order Caudovirales, these tailed phages are best defined as members of the class Caudoviricetes, with taxonomic uncertainty prevailing at more granular taxa. In order to determine the epistemological value of genome topology in the context of the human gut virome, we designed a set of seven experiments to assay the impact of genome topology and representative viral selection on biological interpretation. Using Oxford Nanopore long reads for viral genome assembly coupled with Illumina short read polishing, we show that circular and linear virus genomes differ remarkably in terms of genome quality, GC-skew, tRNA gene frequency, structural variant frequency, cross-reference functional annotation (COG, KEGG, Pfam, and TIGRfam), state-of-the-art marker-based classification, and phage-host interaction. The disparity profile furthermore changes during dereplication. In particular, our phage-host interaction results demonstrate that proportional abundances are incomparable without due regard for genome topology and dereplication threshold, which necessitates the need for standardized reporting. As a best practice guideline, we recommend that comparative studies of the human gut virome should report the ratio of circular to linear viral genomes (ΔCL) along with the dereplication threshold so that structural and functional metrics can be placed into context when assessing biologically relevant metagenomic properties such as proportional abundance.
AI Algorithm Deployment and Utilization: Strategies to Facilitate Clinical Workflow Implementation and Integration
Authors: Erdal Barbaros Selnur , Laugerette Alexis , Fair Kimberly H. , Zimmermann Mathis , Demirer Mutlu , Gupta Vikash , O’Donnell Thomas P. , White Richard D. 
Published: September 2023

AbstractBased on past experiences of the Center for Augmented Intelligence in Imaging (CAII) [Department of Radiology, Mayo Clinic Florida], depending on the project, 10 to 20 months has typically been required to realize the successful creation (data curation and algorithm development), and utilization (integration, testing, and operationalization) of an AI algorithm [Figure 1].Abstract FigureFigure 1:AI algorithm evolution typically requires 10 to 20 months, consisting of four consecutive phases: 1. data identification and extraction; 2. data cleansing and labeling; 3. algorithm development with training and tuning; and 4. Implementation and integration with testing and operationalization.This manuscript delineates the related challenges and opportunities for greater efficiency in completing the clinical workflow implementation and integration of an AI algorithm. Strategies exploiting conventional data standards in facilitating the completion of such deployment and utilization goals within the operations of a busy Radiology practice are described. Methodologies and techniques employed during this initial phase of the CAII-Siemens D&A AI collaboration to address the previously mentioned challenges and opportunities are depicted with use-case examples.
HumanPaenibacillusInfections: A Systematic Review with Comparison of Adult and Infant Cases
Authors: Smith Danielle , Bastug Kristen , Burgoine Kathy , Broach James R. , Hehnly Christine , Morton Sarah U. , Osman Marwan , Schiff Steven J. , Ericson Jessica E. 
Published: September 2023

AbstractNeonatal infections due toPaenibacillus specieshave increasingly been reported over the last few years. We performed a structured literature review of humanPaenibacillusinfections in infants and adults to compare the epidemiology of infections between these distinct patient populations. Thirty-nine reports describing 176 infections met our inclusion criteria and were included. There were 37Paenibacillusinfections occurring in adults caused by 23 species. The clinical presentations of infections were quite variable. In contrast, infections in infants were caused by only 3 species:P. thiaminolyticus(112/139, 80%),P. alvei(2/139, 1%) andP. dendritiformis(2/139, 1%). All of the infants withPaenibacillusinfection presented with a sepsis syndrome or meningitis, often complicated by extensive cerebral destruction and hydrocephalus. Outcomes were commonly poor with 17% (24/139) mortality. Cystic encephalomalacia due to brain destruction was common in both Ugandan and American cases and 92/139 (66%) required surgical management of hydrocephalus following their infection.Paenibacillusinfections are likely underappreciated in infants and effective treatments are urgently needed.
Endozoicomonasprovides corals with steroid hormones during thermal stress
Authors: Ochsenkühn Michael A. , Mohamed Amin R. , Haydon Trent D. , Coe Lisa S.Y. , Abrego David , Amin Shady A. 
Published: September 2023

Summary ParagraphRising temperatures are devastating coral populations throughout the globe1. The coral microbiome is believed to play a critical role in sustaining corals and enabling their adaptation to environmental changes, particularly thermal stress2–4. A ubiquitous group of coral-associated bacteria, known asEndozoicomonas, are hypothesized to provide their host with essential metabolites5. However, the nature of coral-Endozoicomonassymbiosis and the role these bacteria play in adaptation to thermal stress are largely unknown. Here, we show that symbioticEndozoicomonasadapt to the host environment by gaining the ability to degrade coral-derived steroids andSymbiodiniaceae-derived galactose while losing the ability to synthesize iron-binding siderophores, a common feature of free-living marine bacteria6. More importantly, under thermal stressEndozoicomonasutilizes coral-derived cholesterol partially as a carbon source while simultaneously converting it to the hormones testosterone and progesterone. Both steroids prime the innate immune system and inhibit pathogenic bacteria and fungi7. These findings highlight an unknown interaction between corals and their microbiome that may be critical to coral health as oceans warm up. The ability of bacteria to synthesize eukaryotic steroid hormones underscores the importance of these molecules in inter-kingdom interactions and suggests that their origin may have evolved as a result of eukaryogenesis.
Physical structure and interstitial flows govern microbial life in microenvironments
Authors: Shen Rachel , Borer Benedict , Ciccarese Davide , Salek M. Mehdi , Babbin Andrew R. 
Published: September 2023

AbstractMost microbial life on Earth is found in localized microenvironments that collectively exert a crucial role in maintaining ecosystem health and influencing global biogeochemical cycles. In many habitats such as biofilms in aquatic systems, bacterial flocs in activated sludge, periphyton mats, or particles sinking in the ocean, these microenvironments experience sporadic or continuous flow. Depending on their microscale structure, pores and channels through the microenvironments permit localized flow that shifts the relative importance of diffusive and advective mass transport. How this flow alters nutrient supply, facilitates waste removal, drives the emergence of different microbial niches, and impacts the overall function of the microenvironments remains unclear. Here, we quantify how pores through microenvironments that permit flow can elevate nutrient supply to the resident bacterial community using a microfluidic experimental system and gain further insights from coupled population-based and computational fluid dynamics simulations. We find that the microscale structure determines the relative contribution of advection versus diffusion, and even a modest flow through a pore in the range of 10 µm s−1can increase the carrying capacity of a microenvironment by 10%. Recognizing the fundamental role that microbial hotspots play in the Earth system, developing frameworks that predict how their heterogeneous morphology and potential interstitial flows change microbial function and collectively alter global scale fluxes is critical.
Agtrevirus phage AV101 infect diverse extended spectrum β-lactamaseE. coliby recognizing four different O-antigens
Authors: Sørensen Anders Nørgaard , Kalmar Dorottya , Lutz Veronika Theresa , Klein-Sousa Victor , Taylor Nicholas M. I. , Sørensen Martine C. Holst , Brøndsted Lone 
Published: September 2023

AbstractBacteriophages in theAgtrevirusgenus are known for expressing multiple tail spike proteins (TSPs), but little is known about their genetic diversity and host recognition apart from their ability to infect diverseEnterobacteriaceaespecies. Here we aim to determine the genetic differences that may account for the diverse host ranges ofAgrevirusphages. We performed comparative genomics of 14Agtrevirusand identified only a few genetic differences including genes involved in nucleotide metabolism. Most notably was the diversity of thetspgene cluster, specifically in the receptor binding domains that were unique among most of the phages. We further characterized agtrevirus AV101 infecting nine diverse Extended Spectrum β-lactamase (ESBL)E. coliand demonstrated that this phage encoded four unique TSPs amongAgtrevirus. Purified TSPs formed translucent zones and inhibited AV101 infection of specific hosts, demonstrating that TSP1, TSP2, TSP3, and TSP4 recognize O8, O82, O153, and O159 O-antigens of ESBLE. coli, respectively. BLASTp analysis showed that the receptor binding domain of TSP1, TSP2, TSP3 and TSP4 are similar to TSPs encoded byE. coliprophages and distant related virulent phages. Thus,Agtrevirusmay have gained their receptor binding domains by recombining with prophages or virulent phages. Overall, combining bioinformatic and biological data expands the understanding of TSP host recognition ofAgtrevirusand give new insight into the origin and acquisition of receptor binding domains ofAckermannviridaephages.One sentence summaryAgtrevirus phage AV101 express four unique tail spike proteins that recognize different O-antigens of Extended Spectrum β-Lactamase producingE. coli.
Double-Strand Break Repair Pathways Differentially Affect Processing and Transduction by Dual AAV Vectors
Authors: Maurer Anna C. , Benyamini Brian , Fan Vinson B. , Whitney Oscar N. , Dailey Gina M. , Darzacq Xavier , Weitzman Matthew D. , Tjian Robert 
Published: September 2023

SUMMARYRecombinant adeno-associated viral vectors (rAAV) are a powerful tool for gene delivery but have a limited DNA carrying capacity. Efforts to expand this genetic payload have focused on engineering the vector components, such as dual trans-splicing vectors which double the delivery size by exploiting the natural concatenation of rAAV genomes in host nuclei. We hypothesized that inefficient dual vector transduction could be improved by modulating host factors which affect concatenation. Since factors mediating concatenation are not well defined, we performed a genome-wide screen to identify host cell regulators. We discovered that Homologous Recombination (HR) is inhibitory to dual vector transduction. We demonstrate that depletion or inhibition of HR factors BRCA1 and Rad51 significantly increase reconstitution of a large split transgene by increasing both concatenation and expression from rAAVs. Our results define new roles for DNA damage repair in rAAV transduction and highlight the potential for pharmacological intervention to increase genetic payload of rAAV vectors.
Isolation and characterization of persisters of the pathogenic microorganismStaphylococcus aureus
Authors: Liu Shiqi , Laman Paul , Jensen Sean , van der Wel Nicole N. , Kramer Gertjan , Zaat Sebastian A. J. , Brul Stanley 
Published: September 2023

AbstractStaphylococcus aureusis a notorious pathogen responsible for significant morbidity and mortality in both human society and animal husbandry. The presence ofS. aureuspersisters is also one of the leading causes of recurrent and chronic diseases. Persisters are a subset of growth-arrested bacteria within a susceptible bacterial population that are able to tolerate antibiotic treatment and resuscitate after stress removal. Consequently, investigating their formation and characteristics is of crucial importance to provide mechanism-based options for their eradication. However, one challenge in mechanistic research on persisters is the enrichment of pure persisters. In this work, we validated a proposed method to isolate persisters from vancomycin and enrofloxacin generated persistent populations. With this, we analyzed the proteome profile of pure persisters and revealed the distinct mechanisms associated with vancomycin and enrofloxacin induced persisters. Furthermore, morphological and metabolic characterizations were performed, indicating further differences between these two persister populations. Finally, we assessed the effect of ATP repression, protein synthesis inhibition and reactive oxygen species (ROS) level on persister formation. In conclusion, this work provides a comprehensive understanding ofS. aureusvancomycin and enrofloxacin induced persisters at the molecular, single cell and population levels, facilitating a better understanding of persisters and the development of effective strategies to combat them.
The Arabidopsis U1 snRNP regulates mRNA 3’-end processing
Authors: Mangilet Anchilie F. , Weber Joachim , Schüler Sandra , Droste-Borel Irina , Streicher Samuel , Schmutzer Thomas , Rot Gregor , Macek Boris , Laubinger Sascha 
Published: September 2023

ABSTRACTThe removal of introns by the spliceosome is a key gene regulatory mechanism in eukaryotes, with the U1 snRNP subunit of the spliceosome playing a crucial role in the early stages of splicing. Studies in metazoans show that the U1 snRNP also conducts splicing-independent functions, but the lack of genetic tools and knowledge about U1 snRNP-associated proteins have limited the study of such splicing-independent functions in plants. Here, we describe an RNA-centric approach that identified more than 200 proteins associated with the Arabidopsis U1 snRNP, among them mRNA cleavage and polyadenylation factors. The loss of U1 core components is linked to premature cleavage and polyadenylation within gene bodies and alternative polyadenylation site selection in 3’-UTRs. Overall, our work provides a comprehensive view of U1 snRNP interactors and reveals novel functions in regulating mRNA 3’-end processing in Arabidopsis, thus establishing the groundwork for a better understanding of non-canonical functions of plant U1 snRNPs.
Threatened and Priority listed Melaleuca species from Western Australia display high susceptibility toAustropuccinia psidiiin controlled inoculations
Authors: Martino A. M. , Park R. F. , Tobias P. A. 
Published: September 2023

AbstractAustropuccinia psidiicauses rust disease on species within the family Myrtaceae and was first detected in Australia in 2010, with the first detection in Western Australia in 2022. While species within the genusMelaleucafrom Eastern Australia show variable responses to the pathogen, little is known of the response of species from Western Australia. This study established that 13 previously unscreened species ofMelaleuca, including Threatened and Priority species that were grown from seeds sourced from Western Australian populations, were susceptible to the pandemic strain of the pathogen. The proportion of highly susceptible plants within a single species ranged from 2% – 94%, with several species displaying highly variable levels of resistance toA. psidii. These results highlight the importance of disease screening and may direct conservation efforts.
Model-directed generation of CRISPR-Cas13a guide RNAs designs artificial sequences that improve nucleic acid detection
Authors: Mantena Sreekar , Pillai Priya P. , Petros Brittany A. , Welch Nicole L. , Myhrvold Cameron , Sabeti Pardis C. , Metsky Hayden C. 
Published: September 2023

AbstractGenerating maximally-fit biological sequences has the potential to transform CRISPR guide RNA design as it has other areas of biomedicine. Here, we introduce model-directed exploration algorithms (MEAs) for designing maximally-fit, artificial CRISPR-Cas13a guides—with multiple mismatches to any natural sequence—that are tailored for desired properties around nucleic acid diagnostics. We find that MEA-designed guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared to guides derived directly from natural sequences, and illuminate interpretable design principles that broaden Cas13a targeting.