bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scenarios for the emergence of new miRNA genes in the plantArabidopsis halleri
Authors: Pavan Flavia , Lacoste Eléanore , Castric Vincent , Legrand Sylvain 
Published: July 2024

AbstractMicroRNAs (miRNAs) are central players of the regulation of gene expression in Eukaryotes. The repertoires of miRNA genes vary drastically even among closely related species, indicating that they are evolutionarily labile. However, the processes by which they originate over the course of evolution and the nature of their progenitors across the genome remain poorly understood. Here we analyzed miRNA genes inArabidopsis halleri, a plant species where we recently documented a large number of species-specific miRNA genes, likely to represent recent events of emergence. Analysis of sequence homology across the genome indicates that a diversity of sources contributes to the emergence of new miRNA genes, including inverted duplications from protein-coding genes, rearrangements of transposable element sequences and duplications of preexisting miRNA genes. Our observations indicate that the origin from protein-coding genes was less common than was previously considered. In contrast, we estimate that almost half of the new miRNA genes likely emerged from transposable elements. Miniature inverted transposable elements (MITE) seem to be particularly important contributors to new miRNA genes, with the Harbinger and Mariner transposable element superfamilies representing disproportionate sources for their emergence. We further analyzed the recent expansion of a miRNA family derived from MuDR elements, and the duplication of miRNA genes formed by two hAT transposons. Overall, our results illustrate the rapid pace at which new regulatory elements can arise from the modification of preexisting sequences in a genome, and highlight the central role of certain categories of transposable elements in this process.
The role of dietary patterns in the polarization of angiogenic uterine Natural Killer cells during murine pregnancy
Authors: Salles Evila Lopes , Zavan Bruno , Marcelino Rodolfo Cabral , Chagas Pablo Shimaoka , do Amarante-Paffaro Andrea Mollica , Woodham Padmashree Chaudhury , Baban Babak , Paffaro Junior Valdemar Antonio 
Published: July 2024

AbstractUterine Natural Killer (uNK) cells, predominant leukocytes in mouse and human pregnant uteruses, play crucial roles in angiogenesis and pregnancy protection. In mice, DBA lectin-reactive uNK cells expressing Gal-N-Ac sugar exhibit angiogenic functions essential for pregnancy maintenance. This study compares the impact of different nutritional imbalances on mouse pregnancy and the activation of angiogenic DBA+ uNK cells to safeguard against pregnancy complications. High Fat (HF), High Carbohydrate (HC), High Protein (HP), and Food Restriction (FR) diets were administered from gestation day (GD) 1 to GD10 or until parturition. HF and HC diets led to reduced expression of DBA-identified N-acetyl-D-galactosamine, akin to LPS-induced inflammation, and decreased uNK perforin levels. Additionally, HF and HC diets resulted in elevated endometrial cleaved caspase-3 and decreased smooth muscle alpha-actin, causing blood vessel wall thinning without jeopardizing pregnancy term. FR impaired uNK differentiation, manifesting as an “all-or-none” phenomenon with 50% pregnancy failure. Our findings highlight the intricate relationship between nutritional imbalances and mouse pregnancy outcomes. Notably, high-fat diets elicited pronounced responses from DBA+ uNK cells, while high-protein diets had relatively weaker effects. This study underscores the importance of comprehending uNK cell dynamics in maintaining pregnancy homeostasis under diverse dietary conditions, paving the way for elucidating molecular mechanisms governing these interactions. By shedding light on these complex relationships, this research offers valuable insights for improving maternal and fetal health in the context of nutritional interventions during pregnancy.
The axillary lymphoid organ - an external, experimentally accessible immune organ in the zebrafish
Authors: Castranova Daniel , Kenton Madeleine I. , Kraus Aurora , Dell Christopher W. , Park Jong S. , Galanternik Marina Venero , Park Gilseung , Lumbantobing Daniel N. , Dye Louis , Marvel Miranda , Iben James , Taimatsu Kiyohito , Pham Van , Willms Reegan J. , Blevens Lucas , Robertson Tanner F. , Hou Yiran , Huttenlocher Anna , Foley Edan , Parenti Lynne R. , Frazer J. Kimble , Narayan Kedar , Weinstein Brant M. 
Published: July 2024

AbstractLymph nodes and other secondary lymphoid organs play critical roles in immune surveillance and immune activation in mammals, but the deep internal locations of these organs make it challenging to image and study them in living animals. Here, we describe a previously uncharacterized external immune organ in the zebrafish ideally suited for studying immune cell dynamicsin vivo, the axillary lymphoid organ (ALO). This small, translucent organ has an outer cortex teeming with immune cells, an inner medulla with a mesh-like network of fibroblastic reticular cells along which immune cells migrate, and a network of lymphatic vessels draining to a large adjacent lymph sac. Noninvasive high-resolution imaging of transgenically marked immune cells can be carried out in the lobes of living animals, and the ALO is readily accessible to external treatment. This newly discovered tissue provides a superb model for dynamic live imaging of immune cells and their interaction with pathogens and surrounding tissues, including blood and lymphatic vessels.TeaserA newly characterized external zebrafish lymphoid organ provides a powerful model for live imaging of immune cell dynamics
Human P2X4 receptor gating is modulated by a stable cytoplasmic cap and a unique allosteric pocket
Authors: Shi Haoyuan , Ditter Ismayn A. , Oken Adam C. , Mansoor Steven E. 
Published: July 2024

AbstractP2X receptors (P2XRs) are a family of ATP-gated ion channels comprising homomeric and heteromeric trimers of seven subunits (P2X1– P2X7) that confer different rates of desensitization. The helical recoil model of P2XR desensitization proposes the stability of the cytoplasmic cap sets the rate of desensitization, but timing of its formation is unclear for slow-desensitizing P2XRs. We report cryo-EM structures of full-length, wild-type human P2X4receptor in apo, antagonist-bound, and desensitized states. Because the apo and antagonist-bound structures of this slow-desensitizing P2XR include an intact cytoplasmic cap while the desensitized state structure does not, the cytoplasmic cap forms before agonist binding. Furthermore, structural and functional data suggests the cytoplasmic cap is stabilized by lipids to slow desensitization and that P2X4is further modified by glycosylation and palmitoylation. Finally, our antagonist-bound inhibited state structure reveals features specific to the allosteric ligand-binding pocket in human receptors that empower the development of small-molecule modulators.
A systematic review quantifying host feeding patterns ofCulicoidesspecies responsible for pathogen transmission
Authors: Fairbanks Emma L , Tildesley Michael J , Daly Janet M 
Published: July 2024

AbstractCulicoidesbiting midges are significant vectors of various pathogens, impacting both human and animal health globally. Understanding their host feeding patterns is crucial for deepening our understanding of disease transmission dynamics and developing effective control strategies. While several studies have identified the sources of blood meals inCulicoides, a quantitative synthesis of their host preferences and the factors influencing these behaviours is lacking. A systematic literature search focused on gathering data on (1) host selection and (2) host preference. For reviewing host selection we focused on studies reporting the identification of blood meal sources in individualCulicoides. When reviewing host preference we focused on studies comparing the number ofCulicoidescaught on or nearby different host species at the same location. Analysis revealed that someCulicoidesspecies exhibit fixed host preferences, consistently feeding on specific hosts such as cattle and horses, while others display more opportunistic feeding behaviours. Notable variations were observed across different geographic regions. The findings indicate that host availability significantly influencesCulicoidesfeeding patterns. This study highlights the complexity of host selection inCulicoidesbiting midges, which has implications for disease transmission. The variability in feeding behaviours underscores the need for regional assessments to inform targeted vector control strategies.
Altering rRNA 2’O-methylation pattern during neuronal differentiation is regulated by FMRP
Authors: D’Souza Michelle Ninochka , Gowda Naveen Kumar Chandappa , Hariharan Nivedita , Qadri Syed Wasifa , Palakodeti Dasaradhi , Muddashetty Ravi S 
Published: July 2024

AbstractThe Fragile X Messenger Ribonucleoprotein (FMRP) is a selective RNA-binding protein that localizes to the cytoplasm and the nucleus. The loss of FMRP results in Fragile X Syndrome (FXS), an Autism Spectrum Disorder. FMRP interacts with ribosomes and regulates the translation of mRNAs essential for neuronal development and synaptic plasticity. However, the biochemical nature of this translation regulation is unknown. Here we report that a key feature of FMRP-mediated translation regulation during neuronal differentiation is modulating the 2’O-methylation of ribosomal RNA. 2’O-methylation, facilitated by C/D box snoRNAs in the nucleus, is a major epitranscriptome mark on rRNA, essential for ribosome assembly and function. We found that FMRP influences a distinct rRNA 2’O-Methylation pattern across neuronal differentiation. We show that in H9 ESCs, FMRP interacts with a selected set of C/D box snoRNA in the nucleus resulting in the generation of ribosomes with a distinct pattern of rRNA 2’O-Methylation. This epitranscriptome pattern on rRNA undergoes a significant change during the differentiation of ESCs to neuronal precursors and cortical neurons. ESCs display maximum hypomethylated residues on rRNA, which is eventually reduced in neuronal precursors and post-mitotic cortical neurons and this is correlated to the change in global protein synthesis among the states of differentiation. Importantly, this gradual change in the 2’O-methylation pattern during neuronal differentiation is altered in the absence of FMRP, which could impact neuronal development and contribute to dysregulated protein synthesis observed in Fragile X Syndrome. This also suggests the need for diversity in functional ribosomes during the early stages of development.
The rich evolutionary history of the ROS metabolic arsenal shapes its mechanistic plasticity at the onset of metazoan regeneration
Authors: Vullien Aurore , Amiel Aldine , Baduel Loeiza , Diken Dilara , Renaud Cécile , Vervoort Michel , Röttinger Eric , Gazave Eve 
Published: July 2024

AbstractRegeneration, the ability to restore body parts after injury, is widespread in metazoans; however, the underlying molecular and cellular mechanisms involved in this process remain largely unknown, and its evolutionary history is consequently unresolved. In the last decade, ROS have emerged as shared actors that trigger apoptosis and cell proliferation to drive regenerative success in a few metazoan models. However, it is not known whether the contribution of ROS to regeneration relies on conserved mechanisms in animals.Here we performed a comparative genomic analysis of ROS metabolism actors across metazoans, and carried out a comparative study for the deployment and roles of ROS during regeneration in two different research models: the annelid Platynereis dumerilii and the cnidarian Nematostella vectensis. We established that the vast majority of metazoans possess a core redox kit allowing for the production and detoxification of ROS, and overall regulation of ROS levels. However, the precise composition of the redox arsenal can vary drastically from species to species, suggesting that evolutionary constraints apply to ROS metabolism functions rather than precise actors. We found that ROS are produced during and are necessary for regeneration in both Platynereis and Nematostella. However, we also uncovered different enzymatic activities underlying ROS dynamics, as well as distinct effects of ROS signalling on injury-induced apoptosis and cell proliferation in the two species. We conclude that, while ROS are a robust feature of metazoan regeneration, their production and contribution to this phenomenon may depend on plastic molecular mechanisms.
Cell surface ribonucleoproteins cluster with heparan sulfate to regulate growth factor signaling
Authors: Chai Peiyuan , Perr Jonathan , Kageler Lauren , Lebedenko Charlotta G. , Dias Joao M.L. , Yankova Eliza , Esko Jeffrey D. , Tzelepis Konstantinos , Flynn Ryan A. 
Published: July 2024

AbstractReceptor-ligand interactions govern a wide array of biological pathways, facilitating a cell’s ability to interrogate and integrate information from the extracellular space. Here, using an unbiased genome-wide knockout screen, we identify heparan sulfate proteoglycans (HSPGs) as a major component in the organizational mechanism of cell surface glycoRNA and cell surface RNA binding proteins (csRBPs). Cleavage of mature heparan sulfate chains, knockout ofN-and 6-O-sulfotransferases, overexpression of endo-6-O-sulfatases, or the addition of exogenous heparan sulfate chains with high 2-Osulfation result in marked loss in glycoRNA-csRBP clustering in U2OS cells. Functionally, we provide evidence that signal transduction by HS-dependent growth factors such as VEGF-A165is regulated by cell surface RNAs, and in vitro VEGF-A165, selectively interacts with glycoRNAs. Our findings uncover a new molecular mechanism of controlling signal transduction of specific growth factors across the plasma membrane by the regulated assembly of glycoRNAs, csRBPs, and heparan sulfate clusters.
Eco-Evolutionary Consequences of Selective Exploitation on Metapopulations Illustrated With Atlantic Salmon
Authors: Lamarins Amaïa , Carlson Stephanie M. , Prévost Etienne , Satterthwaite William H. , Buoro Mathieu 
Published: July 2024

AbstractWhile the eco-evolutionary consequences of dispersal and exploitation are increasingly recognized, consideration of these effects and how they interact for management and conservation remains limited. We addressed this gap by examining population exploitation within a metapopulation framework, using Atlantic salmon as a case study. We compared eco-evolutionary consequences of alternative exploitation strategies by incorporating selective exploitation based on life history traits and spatial dimension of exploitation (i.e., whether populations were net exporter or importer of individuals). We used a demo-genetic agent-based model to examine demographic and evolutionary consequences of these strategies across a gradient of population-specific exploitation rates. At the metapopulation scale, we found both lower abundance and earlier sexual maturation with increasing exploitation, particularly when fishing was selective on larger individuals. The spatial selectivity of exploitation had an overall additional detrimental effect on metapopulation performance and fisheries yield, and induced stronger evolutionary changes than when exploitation was evenly spread over all populations. We discuss the implications of metapopulation functioning for species management and how considering dispersal patterns and intensity might change how we apply harvest. Nevertheless, our findings suggest that the safest approach remains to distribute exploitation efforts evenly across all populations, especially in the absence of variation in intrinsic productivity and with the dispersal rates and spatial configuration simulated. However, this strategy might not completely prevent negative consequences at the local scale. Therefore, we advise managers to critically assess the relevance of our results and dispersal assumptions in the specific cases they may have to deal with.
Direct RNA sequencing enables improved transcriptome assessment and tracking of RNA modifications for medical applications
Authors: Hewel Charlotte , Wierczeiko Anna , Miedema Johannes , Hofmann Felix , Weißbach Stephan , Dietrich Vincent , Friedrich Johannes , Holthöfer Laura , Haug Verena , Mündnich Stefan , Schartel Lukas , Jenson Kristi , Diederich Stefan , Sys Stanislav , Butto Tamer , Paul Norbert W , Koch Jonas , Lyko Frank , Kraft Florian , Schweiger Susann , Lemke Edward A , Helm Mark , Linke Matthias , Gerber Susanne 
Published: July 2024

AbstractDirect RNA sequencing (DRS) is a nanopore-based technique for analyzing RNA in its native form, promising breakthroughs in diagnostics and biomarker development. Coupled to RNA002 sequencing chemistry, its clinical implementation has been challenging due to low throughput, low accuracy, and lack of large-scale RNA-modification models. In this study, we evaluate the improvements achieved by pairing the latest RNA004 chemistry with novel modified-base-calling models for pseudouridine andN6-methyladenosine using diverse RNA samples from cell lines, synthetic oligos, and human blood. Finally, we present the first clinical application of DRS by confirming the loss of RNA methylation in a patient carrying truncating mutations in the methyltransferaseMETTL5. Conclusively, the combined use of RNA004 chemistry with the base-calling models significantly improved the throughput, accuracy, and site-specific detection of modifications. From this perspective, we offer an outlook on the potential suitability of DRS for use in routine diagnostics and quality assessments of RNA therapeutics.
The divergence of DHN-derived melanin pathways inMetarhizium robertsii
Authors: Xie Linan , Liu Yang , Zhang Yujie , Chen Kang , Yue Qun , Wang Chen , Dun Baoqing , Xu Yuquan , Zhang Liwen 
Published: July 2024

AbstractThe important role of dihydroxynaphthalene-(DHN) melanin in enhancing fungal stress resistance and its importance in fungal development and pathogenicity are well-established. This melanin also aids biocontrol fungi in surviving in the environment and effectively infecting insects. However, the biosynthetic origin of melanin in the biocontrol agents,Metarhiziumspp., has remained elusive due to the complexity resulting from the divergence of two DHN-like biosynthetic pathways. Through the heterologous expression of biosynthetic enzymes from these two pathways in baker’s yeastSaccharomyces cerevisiae, we have confirmed the presence of DHN biosynthesis inM. roberstii, and discovered a novel naphthopyrone intermediate that can produce a different type of pigment. These two pigment biosynthetic pathways differ in terms of polyketide intermediate structures and subsequent modification steps. Stress resistance studies using recombinant yeast cells have demonstrated that both DHN and its intermediates confer resistance against UV light prior to polymerization; a similar result was observed for its naphthopyrone counterpart. This study contributes to the understanding of the intricate and diverse biosynthetic mechanisms of fungal melanin and has the potential to enhance the application efficiency of biocontrol fungi such asMetarhiziumspp. in agriculture.
CRISPR screens reveal ZBTB17/MIZ1 as a peroxisome regulator
Authors: Liu Hongqin , Chen Xi , Wang Hanlin , Zhuang Guanglei , Zhu Zheng-Jiang , Zhuang Min 
Published: July 2024

ABSTRACTPeroxisomes are integral metabolic organelles involved in both catabolic and anabolic processes in humans, with defects often linked to diseases. The functions of peroxisomes are regulated at transcriptional, translational, and post-translational levels. In this study, we employed the CRISPR/Cas9-based genetic screening of a ubiquitin ligase library to identify regulators of human peroxisomes. We discovered that ZBTB17 (also referred as MIZ1) plays a role in regulating the import of proteins into peroxisomes. Independent of its ubiquitin ligase activity, ZBTB17/MIZ1 operates as a transcription factor to directly modulate the expression of key importer PEX13, thereby influencing the localization of peroxisomal enzymes. Furthermore, metabolomic profiling reveals that the knockdown ofZBTB17orPEX13results in similar metabolic alterations, characterized by downregulated purine synthesis, suggesting that ZBTB17’s role in metabolic regulation likely operates through peroxisomes. Collectively, we identify ZBTB17 as a key regulator of peroxisomal protein import, thereby affecting peroxisomal function and nucleotide metabolism. Our findings provide insights into the multifaceted regulation of peroxisomes in complex human cells and shed light on the molecular mechanisms underlying ZBTB17’s role as a transcriptional regulator.
ChromBERT: Uncovering Chromatin State Motifs in the Human Genome Using a BERT-based Approach
Authors: Lee Seohyun , Lin Che , Chen Chien-Yu , Nakato Ryuichiro 
Published: July 2024

AbstractChromatin states, fundamental to gene regulation and cellular identity, are defined by a unique combination of histone post-translational modifications. Despite their importance, comprehensive patterns within chromatin state sequences, which could provide insights into key biological functions, remain largely unexplored. In this study, we introduce ChromBERT, a BERT-based model specifically designed to detect distinct patterns of chromatin state annotation data sequences. Notably, ChromBERT was pre-trained on promoter regions across a diverse range of epigenomes and subsequently fine-tuned using a dataset from multiple cell lines where RNA-seq data were available, highlighting the model’s ability to discern conserved chromatin state patterns within these regions. In addition to its predictive powers across tasks, evidenced by high AUC scores, ChromBERT provides further analysis through the incorporation of motif clustering using Dynamic Time Warping (DTW). This method enhances the model’s ability to dissect chromatin state sequence motifs, typically involving transcription and enhancer sites. The introduction of motif clustering with DTW into ChromBERT’s workflow is poised to facilitate the discovery of genomic regions linked to novel biological functions, deepening our understanding of chromatin state dynamics.