bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Associated Macrophages Expand Chemoresistant, Ovarian Cancer Stem-Like Cells
Authors: Sharrow Allison C , Ho Madeline , Dua Aakriti , Buj Raquel , Blenman Kim R.M. , Orsulic Sandra , Buckanovich Ronald , Aird Katherine M , Wu Lily 
Published: July 2023

AbstractThe persistence of ovarian cancer stem-like cells (OvCSCs) after chemotherapy resistance has been implicated in relapse. However, the ability of these relatively quiescent cells to produce the robust tumor regrowth necessary for relapse remains an enigma. Since normal stem cells exist in a niche, and tumor-associated macrophages (TAMs) are the highest abundance immune cell within ovarian tumors, we hypothesized that TAMs may influence OvCSC proliferation. To test this, we optimized OvCSC enrichment by sphere culture and in vitro polarization of monocytes to a TAM-like M2 phenotype. Using cocultures that permitted the exchange of only soluble factors, we found that M2 macrophages increased the proliferation of sphere cells. Longer-term exposure (5-7 days) to soluble TAM factors led to retention of some stem cell features by OvCSCs but loss of others, suggesting that TAMs may support an intermediate stemness phenotype in OvCSCs. Although TAM coculture decreased the percentage of OvCSCs surviving chemotherapy, it increased the overall number. We therefore sought to determine the influence of this interaction on chemotherapy efficacy in vivo and found that inhibiting macrophages improved chemotherapy response. Comparing the gene expression changes in OvCSCs cocultured with TAMs to publicly available patient data identified 34 genes upregulated in OvCSCs by exposure to soluble TAM factors whose expression correlates with outcome. Overall, these data suggest that TAMs may influence OvCSC proliferation and impact therapeutic response.
Biogeographic context mediates multifaceted diversity-productivity relationships in island and mainland forests
Authors: Tolmos Maria Laura , Guerrero-Ramirez Nathaly R. , Ameztegui Aitor , Barajas Barbosa Martha Paola , Craven Dylan , Kreft Holger 
Published: July 2023

AbstractAimGrowing evidence suggests that impacts of biodiversity loss on ecosystem functioning and nature’s contributions to people are usually negative, yet the magnitude and direction of these impacts can be variable across naturally-assembled ecosystems. A potential driver of variation in diversity-productivity relationships is the biogeographical context, which may alter these relationshipsviaprocesses acting on the size and composition of the species pool like dispersal limitation, environmental filtering, speciation, and invasibility. However, the extent to which the relationships between biodiversity facets and forest productivity are shaped by the biogeographic context remains uncertain. Here, we examine the effects of taxonomic, phylogenetic, and functional tree diversity on aboveground productivity in climatically similar forests on islands and mainland.LocationContinental and insular Spain.Time period1997-2018.Major taxa studiedTrees.MethodsUsing plot data from a national forest inventory, we assessed the influence of taxonomic, phylogenetic, and functional diversity on aboveground productivity using linear models and structural equation models, while accounting for environmental conditions, non-native species, and the number of trees.ResultsWe find that drier environmental conditions lead to a decrease in productivity and in the number of trees in both island and mainland forests. In island forests, non-native species increased productivity directly andviatheir effects on phylogenetic diversity.Main conclusionsOur results suggest that multifaceted diversity, by capturing the diversity of evolutionary history, contributes to elucidating diversity-productivity relationships in island forests that could not be detected otherwise by taxonomic diversity alone. By filling empty niches in island forests, we find that non-native species are fundamentally altering ecosystem functioning on islands.
Zero-Shot Transfer of Protein Sequence Likelihood Models to Thermostability Prediction
Authors: Reeves Shawn , Kalyaanamoorthy Subha 
Published: July 2023

ABSTRACTProtein sequence likelihood models (PSLMs) are an emerging class of self-supervised deep learning algorithms which learn distributions over amino acid identities in structural and evolutionary contexts. Recently, PSLMs have demonstrated impressive performance in predicting the relative fitness of variant sequences without any task-specific training. In this work, we comprehensively analyze the capacity of six PSLMs to predict experimental measurements of thermostability for variants of hundreds of heterogeneous proteins. We assess performance of PSLMs relative to state-of-the-art supervised models, highlight relative strengths and weaknesses, and examine the complementarity between these models. We focus our analyses on stability engineering applications, assessing which methods and combinations of methods can most consistently identify and prioritize mutations for experimental validation. Our results indicate that structure-based PSLMs have competitive performance with the best existing supervised methods and can augment the predictions of supervised methods by integrating insights from their disparate training objectives.
Fragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF
Authors: Adams Charlotte , Gabriel Wassim , Laukens Kris , Picciani Mario , Wilhelm Mathias , Bittremieux Wout , Boonen Kurt 
Published: July 2023

AbstractImmunopeptidomics plays a crucial role in identifying targets for immunotherapy and vaccine development. Because the generation of immunopeptides from their parent proteins does not adhere to clear-cut rules, rather than being able to use known digestion patterns, every possible protein subsequence within human leukocyte antigen (HLA) class-specific length restrictions needs to be considered during sequence database searching. This leads to an inflation of the search space and results in lower spectrum annotation rates. Peptide-spectrum match (PSM) rescoring is a powerful enhancement of standard searching that boosts the spectrum annotation performance. Low abundant peptides often occur in the field of immunopeptidomics, which is why the highly sensitive timsTOF instruments are increasingly gaining popularity. To improve PSM rescoring for immunopeptides measured using timsTOF instruments, we trained a deep learning-based fragment ion intensity prediction model. 302,105 unique synthesized non-tryptic peptides from the ProteomeTools project were analyzed on a timsTOF-Pro to generate a ground-truth dataset, containing 93,227 MS/MS spectra of 74,847 unique peptides, that was used to fine-tune an existing Prosit model. By applying our fragment ion intensity prediction model, we demonstrate up to 3-fold improvement in the identification of immunopeptides. Furthermore, our approach increased detection of immunopeptides even from low input samples.
Estimation of contemporary effective population size in plant populations: limitations of genomic datasets
Authors: Gargiulo Roberta , Decroocq Véronique , González-Martínez Santiago C. , Paz-Vinas Ivan , Aury Jean-Marc , Lesur Kupin Isabelle , Plomion Christophe , Schmitt Sylvain , Scotti Ivan , Heuertz Myriam 
Published: July 2023

AbstractEffective population size (Ne) is a pivotal evolutionary parameter with crucial implications in conservation practice and policy. Genetic methods to estimateNehave been preferred over demographic methods because they rely on genetic data rather than time-consuming ecological monitoring. Methods based on linkage disequilibrium, in particular, have become popular in conservation as they require a single sampling and provide estimates that refer to recent generations. A recently developed software based on linkage disequilibrium, GONE, looks particularly promising to estimate contemporary and recent-historicalNe(up to 200 generations in the past). Genomic datasets from non-model species, especially plants, may present some constraints to the use of GONE, as linkage maps and reference genomes are seldom available, and SNPs genotyping is usually based on reduced-representation methods. In this study, we use empirical datasets from four plant species to explore the limitations of plant genomic datasets when estimatingNeusing the algorithm implemented in GONE, in addition to exploring some typical biological limitations that may affectNeestimation using the linkage disequilibrium method, such as the occurrence of population structure. We show how accuracy and precision ofNeestimates potentially change with the following factors: occurrence of missing data, limited number of SNPs/individuals sampled, and lack of information about the location of SNPs on chromosomes, with the latter producing a significant bias, previously unexplored with empirical data.
An mRNA-encoded, long-lasting Interleukin-2 restores CD8+T cell neoantigen immunity in MHC class I-deficient cancers
Authors: Beck Jan D. , Diken Mustafa , Suchan Martin , Streuber Michael , Diken Elif , Kolb Laura , Allnoch Lisa , Vascotto Fulvia , Peters Daniel , Beißert Tim , Türeci Özlem , Kreiter Sebastian , Vormehr Mathias , Sahin Ugur 
Published: July 2023

AbstractMHC class I antigen presentation deficiency is considered to be the most prevalent cancer immune escape mechanism. Despite its increasing occurrence, the mechanistic implications, and potential strategies to address this challenge, remain poorly understood. Studying β2-microglobulin (B2M) deficient mouse tumor models, we found that MHC class I loss leads to a substantial immune desertification of the tumor microenvironment (TME) and broad therapeutic resistance to immune-, chemo- and radiotherapy. We show that treatment with long-lasting mRNA-encoded interleukin-2 (IL2) restores an immune cell infiltrated, IFNγ-promoted, highly proinflammatory TME signa-ture, and when combined with a tumor-targeting monoclonal antibody (mAb), can overcome ther-apeutic resistance. Surprisingly, we identified that effectiveness of this treatment is driven by ne-oantigen-specific IFNγ-releasing CD8+T cells that recognize neoantigens cross-presented by TME-resident activated macrophages that under IL2 treatment acquire augmented antigen presen-tation proficiency along with other M1-phenotype-associated features. Our findings highlight the unexpected importance of restoring neoantigen-specific immune responses in the treatment of cancers with MHC class I deficiencies.
Population genomics and epigenomics provide insights into the evolution of facultative asexuality in plants
Authors: Wang Yangzi , Duchen Pablo , Chávez Alexandra , Sree Sowjanya K. , Appenroth Klaus J. , Zhao Hai , Widmer Alex , Huber Meret , Xu Shuqing 
Published: July 2023

SummaryMany organisms, particularly plants, are facultatively asexual. Because asexual reproduction is beneficial for the short term but costly for the long term, during the range expansion, natural selection should act on the genetic controls of asexuality in these facultatively asexual organisms. However, the genomic evidence of natural selection driving asexuality remains scarce, and the evolutionary consequences of facultatively asexuality on the genomic and epigenomic diversity remain controversial. Here, by analyzing population genomes and epigenomes ofSpirodela polyrhiza(L.) Schleid., a facultatively asexual plant that flowers rarely, we show that this plant has the lowest genomic diversity and DNA methylation levels among all studied multicellular eukaryotes. Within species, demographic history and the frequency of asexual reproduction jointly determined intra-specific variations of genomic diversity and DNA methylation levels. Genome-wide scans revealed that multiple genes involved in flowering and embryogenesis were under positive selection, consistent with the hypothesis that natural selection drove the evolution of asexuality during the recent habitat expansions in this plant. Together, these results provide new insights into the evolution of plant reproductive systems and suggest that natural selection can drive the evolutionary changes of asexuality, which in turn alters the levels of genomic and epigenomic diversity.
Reference genome of the antLasius platythorax
Authors: Feldmeyer Barbara , Guiglielmoni Nadège , Kirangwa Joseph , Menzel Florian , Salces-Ortiz Judit , Fernández Rosa , Buena Atienza Elena , Ciofi Claudio , Diroma Maria Angela , Iannucci Alessio , Natali Chiara , Mc Cartney Ann M. , Riess Olaf , Casadei Nicolas , Waldvogel Ann-Marie 
Published: July 2023

AbstractAnts are a highly diversified insect family of the order Hymenoptera, with many fascinating characteristics such as eusociality, chemical communication, farming, or social parasitism. Moreover, ants frequent a wide variety of habitats from dry deserts, grasslands, and savannas to cold temperate forests. The ability of ants to inhabit such diverse habitat ranges demonstrates their adaptability and ecological resilience. However, little is known about the genetic underpinnings of this vast array of traits and their adaptive potential. Here, we generated a high-quality genome assembly for the ant speciesLasius platythoraxusing long-read PacBio HiFi in combination with chromatin conformation capture (Hi-C) sequencing. We successfully assembled the genome into 15 chromosome-level scaffolds ranging from 7.9 to 19.2 Mb and encompassing 204.6 Mb out of 235.3 Mb (total assembly), and a BUSCO score of 86% (Hymenoptera_odb10). Comparative genomics between the two sister species will provide insights into the genomic basis of trait differentiation.
Mutational analysis reveals a novel role for hepatitis C virus NS5A domain I in cyclophilin-dependent genome replication
Authors: Chen Shucheng , Harris Mark 
Published: July 2023

AbstractThe hepatitis C virus (HCV) NS5A protein is comprised of three domains (D1-3). Previously, we observed that two alanine substitutions in D1 (V67A, P145A) abrogated replication of a genotype 2a (JFH-1 isolate) sub-genomic replicon (SGR) in Huh7 cells, but this phenotype was partially restored in Huh7.5 cells. To investigate the mechanism of this difference we extended this analysis to demonstrate that 5 additional residues, surface exposed and proximal to either V67 or P145, exhibited the same phenotype. In contrast, these mutants in a genotype 3a (DBN3a isolate) SGR retained their phenotype in each cell line.The difference between Huh7 and Huh7.5 cells was reminiscent of the observation that cyclophilin (Cyp) inhibitors are more potent against HCV replication in the former and suggested a role for D1 in Cyp dependence. Consistent with this, all JFH-1 and DBN3a mutants exhibited increased sensitivity to cyclosporin A treatment compared to wildtype. Silencing of CypA in Huh7 cells inhibited replication of both JFH-1 and DBN3a. However, in Huh7.5 cells CypA silencing did not inhibit JFH-1 wildtype, but abrogated replication of all the JFH-1 mutants, and both DBN3a wildtype and all mutants. CypB silencing in Huh7 cells had no effect on DBN3a, but abrogated replication of JFH-1. CypB silencing in Huh7.5 cells had no effect on either SGR. These data demonstrate both a direct involvement of NS5A D1 in Cyp-dependent genome replication and functional differences between genotype 2 and 3 NS5A. Lastly, we confirmed that JFH-1 NS5A D1 interacted with CypAin vitro.
Coordinated inheritance of extrachromosomal DNA species in human cancer cells
Authors: Hung King L. , Jones Matthew G. , Wong Ivy Tsz-Lo , Lange Joshua T. , Luebeck Jens , Scanu Elisa , He Britney Jiayu , Brückner Lotte , Li Rui , González Rocío Chamorro , Schmargon Rachel , Dörr Jan R. , Belk Julia A. , Bafna Vineet , Werner Benjamin , Huang Weini , Henssen Anton G. , Mischel Paul S. , Chang Howard Y. 
Published: July 2023

ABSTRACTThe chromosomal theory of inheritance has dominated human genetics, including cancer genetics. Genes on the same chromosome segregate together while genes on different chromosomes assort independently, providing a fundamental tenet of Mendelian inheritance. Extrachromosomal DNA (ecDNA) is a frequent event in cancer that drives oncogene amplification, dysregulated gene expression and intratumoral heterogeneity, including through random segregation during cell division. Distinct ecDNA sequences, herein termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells. However, how multiple ecDNA species within a tumor cell are assorted and maintained across somatic cell generations to drive cancer cell evolution is not known. Here we show that cooperative ecDNA species can be coordinately inherited through mitotic co-segregation. Imaging and single-cell analyses show that multiple ecDNAs encoding distinct oncogenes co-occur and are correlated in copy number in human cancer cells. EcDNA species are coordinately segregated asymmetrically during mitosis, resulting in daughter cells with simultaneous copy number gains in multiple ecDNA species prior to any selection. Computational modeling reveals the quantitative principles of ecDNA co-segregation and co-selection, predicting their observed distributions in cancer cells. Finally, we show that coordinated inheritance of ecDNAs enables co-amplification of specialized ecDNAs containing only enhancer elements and guides therapeutic strategies to jointly deplete cooperating ecDNA oncogenes. Coordinated inheritance of ecDNAs confers stability to oncogene cooperation and novel gene regulatory circuits, allowing winning combinations of epigenetic states to be transmitted across cell generations.
Stimulation-induced cytokine polyfunctionality as a dynamic concept
Authors: Portmann Kevin , Linder Aline , Eyer Klaus 
Published: July 2023

AbstractCytokine polyfunctionality is a well-established concept in immune cells, especially T cells, and their ability to concurrently produce multiple cytokines has been associated with better immunological disease control and subsequent effectiveness during infection and disease. To date, only little is known about the secretion dynamics of those cells, masked by the widespread deployment of mainly time-integrated endpoint measurement techniques that do not easily differentiate between concurrent and sequential secretion. Here, we employed a single-cell microfluidic platform capable of resolving secretion dynamics of individual PBMCs. To study the dynamics of poly-cytokine secretion, as well as the dynamics of concurrent and sequential polyfunctionality, we analyzed the response at different time points afterex vivoactivation. Firstly, we observed simultaneous secretion of cytokines over the measurement time for most stimulants in a subpopulation of cells only. Secondly, polyfunctionality generally decreased with prolonged stimulation times and revealed no correlation with the concentration of secreted cytokines in response to stimulation. However, we observed a general trend towards higher cytokine secretion in polyfunctional cells, with their secretion dynamics being distinctly different from mono-cytokine secreting cells. This study provided insights into the distinct secretion behavior of heterogenous cell populations after stimulation with well-described agents and such a system could provide better understanding for various immune dynamics in therapy and disease.
A novel ILK/STAT3 pathway controls plasticity in a neural stem cell model of glioblastoma
Authors: Loftus Alexander E. P. , Romano Marianna S. , Phuong Anh Nguyen , Muir Morwenna T. , Dawson John C. , Avalle Lidia , Douglas Adam T. , Mort Richard L. , Byron Adam , Carragher Neil O. , Pollard Steven M. , Brunton Valerie G. , Frame Margaret C. 
Published: July 2023

AbstractGlioblastomas (GBM) are driven by malignant neural stem-like cells that display extensive heterogeneity and phenotypic plasticity, which drives tumour progression and therapeutic resistance. Here we show that the nodal extracellular matrix-cell adhesion protein integrin-linked kinase (ILK; a pseudokinase), is a key determinant of phenotypic plasticity and the mesenchymal-like, invasive cell state in mouse GBM stem cells. We found that a novel ILK-STAT3 signalling pathway is required for plasticity that enables the transition of GBM stem cells to an astrocyte-like state bothin vitroandin vivo. GBM cells genetically depleted of ILK become predominantly stabilised in a transcriptionally-defined progenitor-like state that is characterised by lack of response to differentiation cues and constitutive proliferation. Loss of ILK or interference with STAT3 impairs differentiation potential, reducing phenotypic plasticity of tumour cell populations; additionally, ILK loss causes a mesenchymal- to epithelial-like morphological transition and suppression of malignancy-associated features. Our work defines ILK as a central regulator of multiple GBM phenotypes including phenotypic plasticity and mesenchymal state.
“Sigo en lo Mismo”: the impact of papeles on the education of undocumented Latinx migrant and seasonal farmworkers
Authors: Gutiérrez Lorena 
Published: July 2023

PurposeThe purpose of this paper is to explore the impact of documentation on the educational experiences, college readiness and aspirations of undocumented Latinx migrant and seasonal farmworkers.Design/methodology/approachThis ethnographic study was conducted in a High School Equivalency Program at a large university in the Midwest. Data was collected during two semesters across a three-year span. Participants included six Mexican migrant and seasonal farmworkers who were preparing to earn their General Educational Development (GED) diploma. Using the grounded theory, data was collected and analyzed simultaneously where initial and focused coding took place, followed by cross-case analysis.FindingsAnalysis of student interviews, participant observations and in-depth fieldnotes that include the K-12 educational experiences, experiences during and after the High School Equivalency Program reveal that undocumented Latinx migrant and seasonal farmworkers aspire to earn a GED diploma to access a better future inclusive of college. However, the legal liminality, the uncertainty and ambiguity of being undocumented, impacts their educational journey prior to, during and beyond the High School Equivalency Program. Furthermore, undocumented Latinx migrant and seasonal farmworkers are unable to change their material conditions with a GED because of their documentation status.Originality/valueAlthough researchers have studied the education experiences of Latinx migrant and seasonal farmworkers, analysis and consideration of documentation status is missing. This study contributes much needed findings about the impact of documentation status on the educational experiences, college readiness, and aspirations of Latinx migrant and seasonal farmworkers.