bluuebunny/crossref_metadata_2025_split huggingface dataset:
EryDB: a transcriptomic profile database for erythropoiesis and erythroid-related diseases
Authors: Zheng Guangmin , Wu Song , Zhang Zhaojun , Xin Zijuan , Zhang Lijuan , Zhao Siqi , Wu Jing , Liu Yanxia , Li Meng , Ruan Xiuyan , Bao Yiming , Qu Hongzhu , Fang Xiangdong 
Published: December 2023

AbstractErythropoiesis is a finely regulated and complex process that involves multiple transformations from hematopoietic stem cells to mature red blood cells at hematopoietic sites from the embryonic to the adult stages. Investigations into its molecular mechanisms have generated a wealth of expression data, including bulk and single-cell RNA sequencing data. A comprehensively integrated and well-curated erythropoiesis-specific database will greatly facilitate the mining of gene expression data and enable large-scale research of erythropoiesis and erythroid related diseases. Here, we present EryDB, an open-access and comprehensive database dedicated to the collection, integration, analysis, and visualization of transcriptomic data for erythropoiesis and erythroid-related diseases. Currently, the database includes expertly curated quality-assured data of 3,803 samples and 1,187,119 single cells derived from 107 public studies of three species (Homo sapiens,Mus musculus, andDanio rerio), nine tissue types, and five diseases. EryDB provides users with the ability to not only browse the molecular features of erythropoiesis between tissues and species, but also perform computational analyses of single-cell and bulk RNA sequencing data, thus serving as a convenient platform for customized queries and analyses. EryDB v1.0 is freely accessible athttps://ngdc.cncb.ac.cn/EryDB/home.
An Immunological Synapse Formation Between T Regulatory Cells and Cancer-Associated Fibroblasts Promotes Tumor Development
Authors: Varveri Athina , Papadopoulou Miranta , Papadovasilakis Zacharias , Compeer Ewoud B. , Legaki Aigli-Ioanna , Delis Anastasios , Damaskou Vasileia , Boon Louis , Papadogiorgaki Sevasti , Samiotaki Martina , Foukas Periklis G. , Hatzioannou Aikaterini , Alissafi Themis , Dustin Michael L. , Verginis Panayotis 
Published: December 2023

AbstractCancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumor microenvironment, serving diverse functions in tumor progression, invasion, matrix remodeling and resistance to therapy; yet, the precise mechanisms via which CAFs imprint on the anti-tumor immunity remain poorly understood. Extensive molecular characterization revealed an increased heterogeneity in the CAF compartment and proposed an interaction between CAFs and tumor-infiltrating immune cells, which may shape tumor immune evasion. Herein, we describe a synapse formation between α-SMA+CAFs and regulatory T cells (Tregs) in the TME. Foxp3+Tregs were localized close to α-SMA+CAFs in diverse types of tumor models as well as biopsies from melanoma and colorectal cancer patients. Notably, phenotypically tolerogenic α-SMA+CAFs demonstrated the ability to phagocytose and process tumor antigens, instructing Treg movement arrest, activation and proliferation, in an antigen-specific manner. Of interest, α-SMA+CAFs were characterized by the presence of double-membrane structures, resembling autophagosomes, in their cytoplasm, while analysis of single-cell transcriptomic data pointed autophagy and antigen processing/presentation pathways to be enriched in α-SMA-expressing CAF clusters. In a mechanistic view, conditional knockout of the autophagy pathway in α-SMA+CAFs promoted an inflammatory re-programming of CAFs, reduced Treg infiltration, attenuated tumor development, and potentiated the efficacy of immune checkpoint inhibitor immunotherapy. Overall, our findings reveal an immunosuppressive mechanism operating in the TME, which entails the formation of synapses between α-SMA+CAFs and Tregs in an autophagy-dependent fashion and raises the potential for the development of CAF-targeted therapies in cancer.One Sentence Summaryα-SMA+Cancer Associated Fibroblasts process and present tumor antigens via autophagy to form immunological synapses with Foxp3+T regulatory cells in the tumor microenvironment, promoting tumor development.
Biodistribution of DNA-origami nanostructures in live zebrafish embryos with single-cell resolution
Authors: Kolonelou Christina , Bräutigam Lars , Edwards Steven , Engström Enya , Dias José M. , Spratt Joel , Karampelias Christos , Wennmalm Stefan , Brismar Hjalmar , Andersson Olov , Teixeira Ana I. 
Published: December 2023

AbstractDNA origami-based nanotechnology is a versatile tool for exploring fundamental biological questions and holds significant promise for future biomedical applications. However, the development of DNA origami-based therapeutic agents is hindered by the challenge of translatingin vitroperformance into effective applicationsin vivo. Here, we exploit the optical transparency of the embryonic zebrafish to track intravenously injected, fluorescently labelled wireframe DNA origami nanostructures. Our approach integrated long-term, high-resolution imaging of transgenic live embryos with single-cell RNA sequencing, to elucidate the biodistribution of DNA nanostructures over time, up to 3 days post-injection (dpi). Notably, we observed rapid accumulation of nanostructures in the caudal hematopoietic tissue (CHT), akin to the fetal liver in mammals. We tested the effects of coating the nanostructures with an oligolysine PEG copolymer (K-PEG), a widely used strategy to enhance their stability. The K-PEG coating mitigated the accumulation rate in CHT, enabling higher percentages of the nanostructures to engage with other tissues. Additionally, our findings highlighted the pivotal role of scavenger endothelial cells in DNA origami clearance, with K-PEG offering sustained protection for the nanostructures at the CHT. Furthermore, by monitoring DNA origami in a transgenic zebrafish line designed for targeted macrophage ablation, we found that macrophages contribute to nanostructure clearance at later time points. This study introduces a framework for the analyses of the biodistribution and clearance of DNA origami nanostructures in vivo with single cell resolution and establishes a foundation for the investigation of DNA origami-based nanomedicines in animal models.
Sex-Specific DNA-Replication In The Early Mammalian Embryo
Authors: Halliwell Jason Alexander , Martin-Gonzalez Javier , Hashim Adnan , Dahl John Arne , Hoffmann Eva Ran , Lerdrup Mads 
Published: December 2023

AbstractThe timing of mammalian DNA replication is crucial for minimizing errors and is influenced locally by genome usage and chromatin states. However, our understanding of replication timing in the unique environment that exists in newly formed mammalian embryos is limited. Here, we performed genome-wide investigations of replication timing in mouse zygotes and 2-cell embryos. We discovered that zygotes lack a conventional replication timing, but a program emerged in 2-cell embryos. Notably, this program differs from embryonic stem cells and shows asynchrony between the parental genomes. We observed late replication of maternal pericentromeric regions and DNA associated with the nuclear lamina in each parental genome, whereas unexpected early replication occurred in regions with histone marks deposited by Polycomb Repressive Complexes on the maternal chromatin. This atypical and asynchronous replication of the two parental genomes may advance our understanding of replication stress in early human embryos and trigger strategies to reduce errors and aneuploidies.
Dissecting the Complexities of Learning With Infinite Hidden Markov Models
Authors: Bruijns Sebastian A. ,   International Brain Laboratory, Bougrova Kcénia , Laranjeira Inês C. , Lau Petrina Y. P. , Meijer Guido T. , Miska Nathaniel J. , Noel Jean-Paul , Pan-Vazquez Alejandro , Roth Noam , Socha Karolina Z. , Urai Anne E. , Dayan Peter 
Published: December 2023

AbstractLearning to exploit the contingencies of a complex experiment is not an easy task for animals. Individuals learn in an idiosyncratic manner, revising their approaches multiple times as they are shaped, or shape themselves, and potentially end up with different strategies. Their long-run learning curves are therefore a tantalizing target for the sort of individualized quantitative characterizations that sophisticated modelling can provide. However, any such model requires a flexible and extensible structure which can capture radically new behaviours as well as slow changes in existing ones. To this end, we suggest a dynamic input-output infinite hidden semi-Markov model, whose latent states are associated with specific components of behaviour. This model includes an infinite number of potential states and so has the capacity to describe substantially new behaviours by unearthing extra states; while dynamics in the model allow it to capture more modest adaptations to existing behaviours. We individually fit the model to data collected from more than 100 mice as they learned a contrast detection task over tens of sessions and around fifteen thousand trials each. Despite large individual differences, we found that most animals progressed through three major stages of learning, the transitions between which were marked by distinct additions to task understanding. We furthermore showed that marked changes in behaviour are much more likely to occur at the very beginning of sessions, i.e. after a period of rest, and that response biases in earlier stages are not predictive of biases later on in this task.
Rapid Prediction of Lipid Interaction Sites on Pleckstrin Homology Domains Using Deep Graph Neural Networks and Molecular Dynamics Simulations
Authors: Le Huray Kyle I.P. , Sobott Frank , Wang He , Kalli Antreas C. 
Published: December 2023

AbstractInteractions between membrane proteins and specific lipid molecules play a major role in cellular biology, but characterizing these interactions can be challenging due to the complexity and physicochemical properties of membranes. Molecular dynamics (MD) simulations allow researchers to predict protein-lipid interaction sites and generate testable models. MD simulations are however computationally expensive and require specialist expertise. In this study, we demonstrate that graph neural networks trained on coarse-grained MD simulation data can predict phosphoinositide lipid interaction sites on Pleckstrin Homology (PH) domain structures, a large family of membrane binding domains. The predictions are comparable to the results of simulations and require only seconds to compute. Comparison with experimental data shows that the model can predict known phosphoinositide interaction sites and can be used to form hypotheses for PH domains for which there is no experimental data. This model is a next generation tool for predicting protein-lipid interactions of PH domains and offers a basis for further development of models applicable to other membrane protein classes.
Internal representation of future interactions in rats
Authors: Dvorakova T , Lobellova V , Manubens-Coda P , Sanchez-Jimenez A , Villacorta-Atienza JA , Stuchlik A , Levcik D 
Published: December 2023

SUMMARYAnimals and humans receive the most critical information from parts of the environment that are immediately inaccessible, possibly only visually explored, and highly dynamic. The brain must effectively process potential interactions between elements in such an environment to make appropriate decisions in critical situations. We trained male Long-Evans rats to discriminate static and dynamic visuospatial stimuli displayed on an inaccessible computer screen. We demonstrated that the rats learned to discriminate dynamic visuospatial stimuli faster, with greater accuracy and shorter reaction time than complementary static stimuli. Furthermore, we provide behavioral evidence indicating that rats internally represent dynamic environments as static maps that capture meaningful future interactions. These observations highlight the ecological importance of dynamic stimuli in the outside world and support previous findings in humans that internal static representations can encapsulate relevant spatiotemporal information of dynamic environments. Such a mechanism would allow animals and humans to process complex time-changing situations neatly.
Genomic analysis ofAncylistes closterii, an enigmatic alga parasitic fungus in the arthropod-associated Entomophthoromycotina
Authors: Seto K , James TY 
Published: December 2023

AbstractRecent advances in fungal genome sequencing have dramatically altered our understanding of the phylogeny and evolution of Fungi. However, there are still many poorly studied obligate parasitic or symbiotic fungi for which we lack any genomic information or knowledge of where they fit in the fungal phylogeny.Ancylistes,an endoparasite of desmid green algae, is such an understudied fungal genus. This genus has been taxonomically placed in the group of arthropod pathogens and saprobes, Entomophthoromycotina in Zoopagomycota. Understanding the phylogenetic position ofAncylistesprovides insights into the nutritional evolution of Zoopagomycota, which is primarily composed of animal-associated fungi. In this study, we found and cultivatedAncylistes closteriiwith its hostClosteriumsp. and sequenced its genome to investigate its phylogenetic position and evolution. Phylogenetic analyses using rDNA and genome-scale datasets showed thatA. closteriiwas sister to other Entomophthoromycotina fungi, confirming the taxonomic position ofAncylistes. Despite the ecological distinctiveness betweenAncylistesand other Entomophthoromycotina fungi, our comparative genomic analyses revealed many shared traits of these fungi such as lineage-specific subtilases and hybrid histidine kinases.Ancylistesalso possessed unique genes among Zoopagomycota fungi, such as plant cell wall degrading enzymes which could be important for infection of algae.SignificanceImproved taxon sampling is important for inferring a robust phylogeny of Fungi. However, there are still poorly studied obligate parasitic taxa whose DNA sequencing is challenging, especially in Zoopagomycota, one of the early diverging lineages of Fungi. This study focused on a long-neglected algal parasite,Ancylistes closterii, which belongs to the arthropod-associated group, Entomophthoromycotina. We rediscoveredA. closteriiand established a dual culture of fungus and its host alga, which enabled the first molecular analysis of this enigmatic parasite. Our results provide new insights into the nutritional evolution of primarily animal-associated Zoopagomycota.
Optimization of chondroitin production inE. coliusing genome scale models
Authors: Couto Márcia R. , Rodrigues Joana L. , Braga Adelaide , Dias Oscar , Rodrigues Lígia 
Published: December 2023

AbstractChondroitin is a natural occurring glycosaminoglycan with applications as a nutraceutical and pharmaceutical ingredient and can be extracted from animal tissues. Microbial chondroitin-like polysaccharides emerged as a safer and more sustainable alternative source. However, chondroitin titers using either natural or recombinant microorganisms are still far from meeting the increasing demand. The use of genome-scale models and computational predictions can assist the design of microbial cell factories with possible improved titers of these value-added compounds. Genome-scale models have been used to predict genetic modifications inEscherichia coliengineered strains that would potentially lead to improved chondroitin production. Additionally, using synthetic biology approaches, a pathway for producing chondroitin has been designed and engineered inE. coli. Afterwards, the most promising mutants identified based on bioinformatics predictions were constructed and evaluated for chondroitin production in flask fermentation. This resulted in the production of 118 mg/L of extracellular chondroitin by overexpressing both superoxide dismutase (sodA) and a lytic murein transglycosylase (mltB). Then, batch and fed-batch fermentations at bioreactor scale were also evaluated, in which the mutant overexpressingmltBled to an extracellular chondroitin production of 427 mg/L and 535 mg/L, respectively. The computational approach herein described identified several potential novel targets for improved chondroitin biosynthesis, which may ultimately lead to a more efficient production of this glycosaminoglycan.
A diverse proteome is present and enzymatically active in metabolite extracts
Authors: House Rachel (Rae) J. , Soper-Hopper Molly T. , Vincent Michael P. , Ellis Abigail E. , Capan Colt D. , Madaj Zachary B. , Wolfrum Emily , Isaguirre Christine N. , Castello Carlos D. , Johnson Amy B. , Galvis Martha L. Escobar , Williams Kelsey S. , Lee Hyoungjoo , Sheldon Ryan D. 
Published: December 2023

AbstractMetabolomics, a foundational tool in metabolism research, relies on the accurate transmittal of biochemical profiles underlying biological phenotypes. Over the years, workflows used in metabolomics have been assumed to remove enzymes to preserve metabolite levels during processing. Here, we uncover a diverse landscape of over 1,000 proteins, strongly enriched for metabolic enzymes, within metabolite extracts generated using common extraction workflows. Moreover, by combining in-extract stable isotope additions and enzyme inhibitors, we demonstrate transaminase activity, which is preventable by protein removal by 3 kDa filtration. We extend these findings to untargeted metabolomics, revealing that both post-extraction formation of glutamate dipeptide and depletion of total glutathione can also be prevented by removing proteins. Finally, we present a simple yet novel workflow that integrates passive filtration for protein removal of crude metabolite extracts as a superior method for broad-coverage metabolomics. Our findings have broad-reaching experimental implications across all fields that use metabolomics and molecular metabolism, especially cancer, immunology, and diabetes research.
Genome size and ploidy of the German species ofVeronicaL. (Plantaginaceae)
Authors: Albach Dirk C. , Daubert Mareike 
Published: December 2023

AbstractChromosome numbers and genome size estimates provide essential information for the differentiation of plant species. Especially, closely related species that are morphologically difficult to distinguish are often easily distinguishable by genome size. Flow cytometry has facilitated in recent years the detection of such differentiation at the genomic level. It further helped understand the distribution of ploidy levels within species. The genusVeronicaincludes 37 species in Germany including some taxonomically challenging species groups and some species with intraspecific variation in ploidy. We, here, present 36 new genome size estimates and 44 estimates of ploidy, six and seven, respectively, from Germany, for these 37 species. Estimates ofV. aphylla, V. alpina, V. fruticans, andV. fruticulosaare first estimates for the species. These estimates provide an important basis for future studies on the genus. Some examples are discussed in more details, such as the distribution of ploidy levels inV. longifoliaandV. chamaedrysin Germany or the importance to study ploidy levels inV. satureiifoliaand relatives in southwestern Germany.
Optimising age-specific insulin signalling to slow down reproductive ageing increases fitness in different environments
Authors: Sultanova Zahida , Shen Aykut , Hencel Katarzyna , Carlsson Hanne , Crighton Zoe , Clifton Daniel , Akay Alper , Maklakov Alexei A. 
Published: December 2023

SummaryThe developmental theory of ageing proposes that age-specific decline in the force of natural selection results in suboptimal levels of gene expression in adulthood, leading to functional senescence. This theory explicitly predicts that optimising gene expression in adulthood can ameliorate functional senescence and improve fitness. Reduced insulin/IGF-1 signalling (rIIS) extends the reproductive lifespan ofCaenorhabditis elegansat the cost of reduced reproduction. Here, we show that adulthood-only rIIS improves late-life reproduction without any detrimental effects on other life-history traits in both benign and stressful conditions. Remarkably, we show that rIIS additively extends late-life reproduction and lifespan when animals are exposed to a fluctuating food environment – intermittent fasting (IF) – resulting in reduced food intake in early adulthood. Full factorial genome-wide RNA-Seq across the life course demonstrated that IF and rIIS modulate the age-specific expression of pro-longevity genes. IF, rIIS and combined IF + rIIS treatment downregulated genes involved in peptide metabolism in early life and differentially regulated immunity genes in later life. Importantly, combined IF + rIIS treatment uniquely regulated a large cluster of genes in mid-life that are associated with immune response. These results suggest that optimising gene expression in adulthood can decelerate reproductive ageing and increase fitness.
Genomic resources forMacadamia tetraphyllaand an examination of its historic use as a crop resource in Hawaii
Authors: Bartlett Bjarne , Cho Alyssa , Laspisa Daniel , Gore Michael A. , Kantar Michael 
Published: December 2023

AbstractMacadamia tetraphyllais a wild relative of the economically valuable cropMacadamia integrifolia. Genomic knowledge of crop wild relatives is central to determining their possible role in breeding programs to mitigate biotic and abiotic stress in the future. The goal of this project was to develop a genomic resource for macadamia agriculture in Hawai‘i through constructing a transcriptome ofM. tetraphyllaand testing for hybridity in University of Hawai‘i at Mānoa breeding material. The transcriptome assembly ofM. tetraphyllarevealed large differences in gene expression attributable to tissue type. Advanced breeding lines (HI862 and HI879) appear to be hybridized with the crop wild relativeM. tetraphylla. Additionally, a putativeM. tetraphyllatree sampled from a remnant orchard planting at the Waimānalo research station on Oahu did not match anecdotal accounts of the orchard as it appeared to be of hybrid ancestry.
Autism genes converge on microtubule biology and RNA-binding proteins during excitatory neurogenesis
Authors: Sun Nawei , Teyssier Noam , Wang Belinda , Drake Sam , Seyler Meghan , Zaltsman Yefim , Everitt Amanda , Teerikorpi Nia , Willsey Helen Rankin , Goodarzi Hani , Tian Ruilin , Kampmann Martin , Willsey A. Jeremy 
Published: December 2023

SummaryRecent studies have identified over one hundred high-confidence (hc) autism spectrum disorder (ASD) genes. Systems biological and functional analyses on smaller subsets of these genes have consistently implicated excitatory neurogenesis. However, the extent to which the broader set of hcASD genes are involved in this process has not been explored systematically nor have the biological pathways underlying this convergence been identified. Here, we leveraged CROP-Seq to repress 87 hcASD genes in a humanin vitromodel of cortical neurogenesis. We identified 17 hcASD genes whose repression significantly alters developmental trajectory and results in a common cellular state characterized by disruptions in proliferation, differentiation, cell cycle, microtubule biology, and RNA-binding proteins (RBPs). We also characterized over 3,000 differentially expressed genes, 286 of which had expression profiles correlated with changes in developmental trajectory. Overall, we uncovered transcriptional disruptions downstream of hcASD gene perturbations, correlated these disruptions with distinct differentiation phenotypes, and reinforced neurogenesis, microtubule biology, and RBPs as convergent points of disruption in ASD.