bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering the Structural and Functional Implications of Uncharacterized NSPs and Variations in the Molecular Toolkit Across Mammalian and Non-Mammalian Arteriviruses
Authors: Siuli Rakesh , Behera Kshitij , Krishnan Arunkumar 
Published: December 2024

AbstractDespite considerable scrutiny of mammalian arterivirus genomes, their genomic architecture remains incomplete, with several unannotated non-structural proteins (NSPs) and the puzzling absence of methyltransferase (MTase) domains. Additionally, the host range of arteriviruses has expanded to include seven newly sequenced genomes from non-mammalian hosts, which remain largely unannotated and await detailed comparisons alongside mammalian isolates. Utilizing comparative genomics approaches and comprehensive sequence-structure analysis, we provide enhanced genomic architecture and annotations for arterivirus genomes. We identify the previously unannotated C-terminal domain of NSP3 as a winged helix-turn-helix domain and classified NSP7 as a new small β-barrel domain, both likely involved in interactions with viral RNA. NSP12 is identified as a derived variant of the N7-MTase-like Rossmann fold domain, showing structural alignment with N7-MTases in Nidovirales, yet it likely lacks enzymatic functionality due to the erosion of catalytic residues, indicating a unique role-specific to mammalian arteriviruses. In contrast, non-mammalian arteriviruses sporadically retain a 2ʹ O-MTase and an exonuclease domain, which are typically absent in mammalian arteriviruses, highlighting contrasting evolutionary trends and variations in their molecular armory. Similar lineage-specific paterns are observed in the diversification of papain-like proteases and structural proteins. Overall, the study extends our knowledge of arterivirus genomic diversity and evolution.
Sparse dimensionality reduction for analyzing single-cell-resolved interactions
Authors: Brunn Niklas , Hackenberg Maren , Vogel Tanja , Binder Harald 
Published: December 2024

AbstractSummarySeveral approaches have been proposed to reconstruct interactions between groups of cells or individual cells from single-cell transcriptomics data, leveraging prior information about known ligand-receptor interactions. To enhance downstream analyses, we present an end-to-end dimensionality reduction workflow, specifically tailored for single-cell cell-cell interaction data. In particular, we demonstrate that sparse dimensionality reduction can pinpoint specific ligand-receptor interactions in relation to clusters of cell pairs. For sparse dimensionality reduction, we focus on the Boosting Autoencoder approach (BAE). Overall, we provide a comprehensive workflow, including result visualization, that simplifies the analysis of interaction patterns in cell pairs. This is supported by a Jupyter notebook that can readily be adapted to different datasets.Availability and implementationhttps://github.com/NiklasBrunn/Sparse-dimension-reductionContactniklas.brunn@uniklinik-freiburg.deSupplementary material…
Circular RNA - circCLIP2 is predominantly expressed in GSC niche and enhances glioblastoma aggressiveness via EMT and ECM signaling
Authors: Misiorek Julia , Zarębska Żaneta , Kuczyński Konrad , Latowska-Łysiak Julia , Grabowska Adriana , Głodowicz Paweł , Sajek Marcin Piotr , Karlik Anna , Wronka Dorota , Barciszewska Anna Maria , Przybył Łukasz , Rolle Katarzyna 
Published: December 2024

AbstractGlioblastoma (GBM) is the most common and malignant type of brain tumor in adults and no effective therapies exist to combat this disease. Surgical resection, radio- and temozolomide-based-chemotherapy are insufficient mainly due to inter- and intra-tumoral heterogeneity of GBM tumors, therefore personalized approaches are required. Additionally, diverse tumor microenvironment with a leading role of glioblastoma stem cells (GSCs) in hypoxic core underlie the aggressiveness and recurrence of GBM. However, the molecules and pathways which directly promote tumor aggressiveness together with the driving process of epithelial-to-mesenchymal transition (EMT) and the components of extracellular matrix (ECM), remain only partially covered with prior studies focused mainly on coding oncogenes and tumor suppressor genes. Over the past years, a special attention has been paid to non-coding, circular RNAs (circRNAs) differentially expressed in various cancers, including GBM. Despite high abundance and stability, the exact biological roles of most individual circRNAs have not been fully revealed, so far. Besides anti-cancer targets, circRNAs have been considered as essential biomarkers and stratifying criterion of malignancy. Thus, studies on functions of differentially expressed circRNAs in GBM are an emerging field to be explored. In herein study, the biological role of circRNA CLIP2 (circCLIP2) was found highly overexpressed in primary tumor tissues. Upon the knock-down of circCLIP2 in 2D and 3Din vitromodels, functional tests performed clearly indicate a significant contribution of circCLIP2 to aggressive potential of GBM as showed by decreased rates of proliferation, migration and invasion. Additional studies indicated predominant expression of circCLIP2 in GSC fractions additionally elevated by hypoxic conditions. The increased rates of proliferation and migration as well as molecular analyses were also confirmed inin vivosettings where xenograft model was applied. The expression of EMT markerSnail2and ECM-degrading enzyme metalloproteinase 9 (MMP9) were significantly downregulated in the tumors formed from circCLIP2 silenced cells. Taken together, these results indicate a strong contribution of circCLIP2 in the aggressive phenotype of GBM which is due to a modulation of GSC proliferative potential as well as migration and invasion via EMT together with the modulator of ECM composition.
Transcutaneous afferent patterned stimulation reduces essential tremor symptoms through modulation of neural activity in the ventral intermediate nucleus of the thalamus
Authors: Luu Cuong P. , Ranum Jordan , Youn Youngwon , Perrault Jennifer L. , Krause Bryan , Banks Matthew , Buyan-Dent Laura , Ludwig Kip A. , Lake Wendell B. , Suminski Aaron J. 
Published: December 2024

AbstractEssential tremor (ET), the most common movement disorder in adults, presents with involuntary shaking of the arms during postural hold and kinetic tasks linked to dysfunction in the cerebello-thalamo-cortical (CTC) network. Recently, transcutaneous afferent patterned stimulation (TAPS), applied through a wrist-worn device, has emerged as a non-invasive therapy for medication refractory ET. However, its mechanism remains unclear. We hypothesize that TAPS reduces tremor through modulation of the VIM thalamus in the CTC network. Employing refractory ET patients seeking VIM deep brain stimulation (DBS), we quantified clinical tremor improvement following TAPS treatment in a pre-operative setting, followed by intra-operative, microelectrode recording of the contralateral thalamus with concurrent TAPS treatment on and off. After one preoperative session, TAPS significantly reduces upper limb tremor, with asymmetric effect favoring the treated limb and greatest improvement tending to kinetic tremor. The magnitude of TAPS-related tremor reduction demonstrates a positive correlation with the modulation of alpha and beta band LFPs in the VIM. TAPS also modulated spiking activity in the VIM, though it was uncorrelated with the degree of tremor reduction. Of note, TAPS related modulation of LFPs and spiking activity was greatest near the optimal placement location for DBS lead in treating ET. In sum, TAPS likely reduces tremor in ET by modulating the VIM and connected nodes in the cerebello-thalamo-cortical pathway.
Characterising the 2023 chikungunya outbreak in Paraguay and the potential impact of a vaccine campaign
Authors: Pérez-Estigarribia Pastor E , Ribeiro dos Santos Gabriel , Cauchemez Simon , Vazquez Cynthia , Ibarrola-Vannucci Ana Karina , Sequera Guillermo , Villalba Shirley , José Ortega María , Luis Di Fabio Jose , Scarponi Danny , Mukandavire Christinah , Deol Arminder , Cabello Águeda , Vargas Elsi , Fernández Cyntia , León Liz , Salje Henrik 
Published: December 2024

AbstractThere now exists a licensed chikungunya vaccine, however, it remains unclear if it could be deployed during outbreaks to reduce the health burden. We used an epidemic in Paraguay as a case study. We conducted a seroprevalence study and used models to reconstruct epidemic transmission dynamics, providing a framework to assess the theoretical impact of a vaccine had it been available. We estimated 33.0% (95% CI: 30.1-36.0) of the population became infected during the outbreak, 6.3% (95%CI: 5.8-6.9) of which were detected by the surveillance system, with a mean infection fatality ratio of 0.013 % (95%CI: 0.012-0.014). A disease-blocking vaccine with 75% efficacy deployed in 40% of > 12-year-olds over a three-month period would have prevented 34,200 (95% CI: 30,900-38,000) cases, representing 23% of cases, and 73 (95%CI: 66-81) deaths. If the vaccine also leads to infection blocking, 88% of cases would have been averted. These findings suggest the vaccine is an important new tool to control outbreaks.
Jumping plant-lice of the tribe Paurocephalini (Hemiptera: Psylloidea: Liviidae) in Brazil
Authors: Serbina Liliya š. , Malenovský Igor , Queiroz Dalva L. , Burckhardt Daniel 
Published: December 2024

AbstractThe predominantly tropical tribe Paurocephalini of jumping plant-lice currently consists of seven genera and 94 described species worldwide, of which the generaKlyveriaBurckhardtet al. andMelanasteraSerbinaet al. have been recorded from Brazil with two and one species, respectively. Here we review the taxonomy of the Brazilian species based on material collected from extensive fieldwork carried out in 15 states over the last decade. One species ofKlyveriaand 59 species ofMelanasteraare newly described, bringing the number of extantKlyveriaspp. to three (both in Brazil and worldwide) and that of extantMelanasteraspp. to 69 (60 in Brazil, 67 in the Neotropical region and one each in the Afrotropical and Oriental regions). The new species are described and illustrated, and identification keys for the Brazilian species are provided for adults and last instar immatures. The most diagnostically important structures are the distal segment of the aedeagus and the paramere, the forewing (shape, venation, surface spinules and colour pattern) and the female terminalia in the adults, and the chaetotaxy, tarsal arolium and shape of the additional pore fields on the caudal plate in the last instar immatures. The species descriptions are complemented by mitochondrial DNA barcodes (COIandcytB) and information on host plants.Klyveriaspp. are restricted toLuehea(Malvaceae), while in Brazil 28Melanasteraspp. develop or are likely to develop on Melastomataceae, 18 spp. on Annonaceae, four spp. each on Asteraceae and Myristicaceae, and one species on Cannabaceae. Only three of the 63 species of Paurocephalini reported here from Brazil, are also known from other countries: two from Paraguay and one from Trinidad. Probably many more species ofMelanasteraare yet to be discovered and described. Priority in fieldwork should be given to areas that are at high risk of destruction or degradation by human activities, such as the Amazon rainforest, the Atlantic Forest and the Cerrado.
Balancing Locality and Reconstruction in Protein Structure Tokenizer
Authors: Zhang Jiayou , Meynard-Piganeau Barthelemy , Gong James , Cheng Xingyi , Luo Yingtao , Ly Hugo , Song Le , Xing Eric 
Published: December 2024

AbstractThe structure of a protein is crucial to its biological function. With the expansion of available protein structures, such as those in the AlphaFold Protein Structure Database (AFDB), there is an increasing need for efficient methods to index, search, and generate these structures. Additionally, there is a growing interest in integrating structural information with models from other modalities, such as protein sequence language models. We present a novel VQ-VAE-based protein structure tokenizer, AIDO.StructureTokenizer (AIDO.St), which is a pretrained module for protein structures in an AI-driven Digital Organism [1]. AIDO.StructureTokenizer is a 300M parameter model consisting of an equivariant encoder to discretize input structures into tokens, and an invariant decoder to reconstruct the inputs from these tokens. In addition to evaluating structure reconstruction ability, we also compared our model to Foldseek, ProToken, and ESM3 in terms of protein structure retrieval ability. Through our experiments, we discovered an intriguing trade-off between the encoder’s locality and retrieval ability and the decoder’s reconstruction ability. Our results also demonstrate that a better balance between retrieval and reconstruction enables a better alignment between the structure tokens and a protein sequence language model, resulting in better structure prediction accuracy. Models and code are available through ModelGenerator inhttps://github.com/genbio-ai/AIDOand onHugging Face.
SynapseNet: Deep Learning for Automatic Synapse Reconstruction
Authors: Muth Sarah , Moschref Frederieke , Freckmann Luca , Mutschall Sophia , Hojas-Garcia-Plaza Ines , Bahr Julius N. , Petrovic Arsen , Thao Do Thanh , Schwarze Valentin , Archit Anwai , Weyand Kirsten , Michanski Susann , Maus Lydia , Imig Cordelia , Brose Nils , Wichmann Carolin , Fernandez-Busnadiego Ruben , Moser Tobias , Rizzoli Silvio O. , Cooper Benjamin H. , Pape Constantin 
Published: December 2024

AbstractElectron microscopy is an important technique for the study of synaptic morphology and its relation to synaptic function. The data analysis for this task requires the segmentation of the relevant synaptic structures, such as synaptic vesicles, active zones, mitochondria, presynaptic densities, synaptic ribbons, and synaptic compartments. Previous studies were predominantly based on manual segmentation, which is very time-consuming and prevented the systematic analysis of large datasets. Here, we introduce SynapseNet, a tool for the automatic segmentation and analysis of synapses in electron micrographs. It can reliably segment synaptic vesicles and other synaptic structures in a wide range of electron microscopy approaches, thanks to a large annotated dataset, which we assembled, and domain adaptation functionality we developed. We demonstrated its capability for (semi-)automatic biological analysis in two applications and made it available as an easy-to-use tool to enable novel data-driven insights into synapse organization and function.
Draft genome and transcriptomic sequence data of three invasive insect species
Authors: Lombaert Eric , Klopp Christophe , Blin Aurélie , Annonay Gwenolah , Iampietro Carole , Lluch Jérôme , Sallaberry Marine , Valière Sophie , Poloni Riccardo , Joron Mathieu , Deleury Emeline 
Published: December 2024

AbstractCydalima perspectalis(the box tree moth),Leptoglossus occidentalis(the western conifer seed bug), andTecia solanivora(the Guatemalan tuber moth) are three economically harmful invasive insect species. This study presents their genomic and transcriptomic sequences, generated through whole-genome sequencing, RNA-seq transcriptomic data, and Hi-C sequencing. The resulting genome assemblies exhibit good quality, providing valuable insights into these species. The genome size are 469.1 Mb forC. perspectalis, 1.77 Gb forL. occidentalis, and 601.7 Mb forT. solanivora. These datasets are available in the NCBI Sequence Read Archive (BioProject PRJNA1140410) and serve as essential resources for population genomics studies and the development of effective pest management strategies, addressing significant gaps in the understanding of invasive insect species.
Essential genes encoded by the mating-type locus of the human fungal pathogenCryptococcus neoformans
Authors: Bian Zhuyun , Xu Ziyan , Peer Anushka , Choi Yeseul , Priest Shelby J. , Akritidou Konstantina , Dasgupta Ananya , Dahlmann Tim A. , Kück Ulrich , Nowrousian Minou , Sachs Matthew S. , Sun Sheng , Heitman Joseph 
Published: December 2024

ABSTRACTFungal sexual reproduction is controlled by the mating-type (MAT) locus. In contrast to a majority of species in the phylum Basidiomycota that have tetrapolar mating-type systems, the opportunistic human pathogenCryptococcus neoformansemploys a bipolar mating-type system, with two mating types (aand α) determined by a singleMATlocus that is unusually large (∼120 kb) and contains more than 20 genes. While severalMATgenes are associated with mating and sexual development, others control conserved cellular processes (e.g. cargo transport and protein synthesis), of which five (MYO2,PRT1,RPL22,RPL39, andRPO41) have been hypothesized to be essential. In this study, through genetic analysis involving sporulation of heterozygous diploid deletion mutants, as well as in some cases construction and analyses of conditional expression alleles of these genes, we confirmed that with the exception ofMYO2, both alleles of the other fourMATgenes are indeed essential for cell viability. We further showed that whileMYO2is not essential, its function is critical for infectious spore production, faithful cytokinesis, adaptation for growth at high temperature, and pathogenicityin vivo. Our results demonstrate the presence of essential genes in theMATlocus that are divergent between cells of opposite mating types. We discuss possible mechanisms to maintain functional alleles of these essential genes in a rapidly-evolving genomic region in the context of fungal sexual reproduction and mating-type evolution.IMPORTANCESexual reproduction is essential for long-term evolutionary success. Fungal cell type identity is governed by theMATlocus, which is typically rapidly evolving and highly divergent between different mating types. In this study, we show that theaand α alleles of four genes encoded in theMATlocus of the opportunistic human fungal pathogenC. neoformansare essential. We demonstrate that a fifth gene,MYO2, which had been predicted to be essential, is in fact dispensable for cell viability. However, a functionalMYO2allele is important for cytokinesis and fungal pathogenicity. Our study highlights the need for careful genetic analyses in determining essential genes, which is complementary to high-throughput approaches. Additionally, the presence of essential genes in theMATlocus ofC. neoformansprovides insights into the function, maintenance, and evolution of these fast-evolving genomic regions.
IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma
Authors: Karakousi Triantafyllia , Cristaldi Vanessa , Lopes de Oliveira Maria Luiza , Medeiros Geraldo Luiz Henrique , González-Robles Tania J. , da Silva Gabrielle , Breazeale Alec P. , Encarnacion-Rosado Joel , Pozniak Joanna , Kimmelman Alec C. , Ruggles Kelly V. , Chris Marine J. , Chandel Navdeep S. , Lund Amanda W. 
Published: December 2024

SummaryLymphatic vessels play a crucial role in activating anti-tumor immune surveillance but also contribute to metastasis and systemic tumor progression. Whether distinct lymphatic phenotypes exist that govern the switch between immunity and metastasis remains unclear. Here we reveal that cytotoxic immunity normalizes lymphatic function and uncouples immune and metastatic potential. We find that in mice and humans, intratumoral lymphatic vessel density negatively correlates with productive cytotoxic immune responses and identify IFNγ as an intrinsic inhibitor of lymphangiogenesis. Specific deletion of theIfngr1in lymphatic endothelial cells (LECs) greatly expanded the intratumoral lymphatic network and drove the emergence of a tip-like endothelial state, promoting lymph node metastasis but not dendritic cell migration. IFNγ inhibits oxidative phosphorylation, which is required for proliferation and acquisition of the pathologic transcriptional state. Our data indicate that IFNγ induces a phenotypic switch in tumor-associated lymphatic vessels to reinforce canonical immune surveillance and block metastasis.
CellSexID: Sex-Based Computational Tracking of Cellular Origins in Chimeric Models
Authors: Tai Huilin , Li Qian , Wang Jingtao , Tan Jiahui , Lang Ryann , Petrof Basil J. , Ding Jun 
Published: December 2024

AbstractCell tracking in chimeric models is essential yet challenging, particularly in developmental biology, regenerative medicine, and transplantation studies. Existing methods, such as fluorescent labeling and genetic barcoding, are technically demanding, costly, and often impractical for dynamic, heterogeneous tissues. To address these limitations, we propose a computational framework that leverages sex as a surrogate marker for cell tracking. Our approach uses a machine learning model trained on single-cell transcriptomic data to predict cell sex with high accuracy, enabling clear distinction between donor (male) and recipient (female) cells in sex-mismatched chimeric models. The model identifies specific genes critical for sex prediction and has been validated using public datasets and experimental flow sorting, confirming the biological relevance of the identified cell populations. Applied to skeletal muscle macrophages, our method revealed distinct transcriptional profiles associated with cellular origins. This pipeline offers a robust, cost-effective solution for cell tracking in chimeric models, advancing research in regenerative medicine and immunology by providing precise insights into cellular origins and therapeutic outcomes.
NJGPT: A Large Language Model-Driven, User-Friendly Solution for Phylogenetic Tree Construction
Authors: Wang Zhixuan , Huang Haoyuan , Li Teng , Rodrigo Allen 
Published: December 2024

AbstractMotivationPhylogenetic reconstruction plays an integral part in much of the research in evolutionary biology. Currently, a newly minted phylogeneticist must choose amongst a relatively large array of phylogenetic software, each often with its own analytical routines, inputs and outputs. Our overarching aim is to construct a user-friendly pipeline with the most recent generative AI tool, ChatGPT-4 (at the time of writing) released by OpenAI, that is able to understand queries written in natural language, to build a phylogenetic tree using sequence data. By doing this, we demonstrate how generative AI may be used in phylogenetics, as a proof-of-concept. We also demonstrate the steps needed, presently, to ensure that ChatGPT can build phylogenetic trees accurately.ResultsWe present NJGPT, a phylogenetic tool built using ChatGPT, a Large Language Model (LLM) Generative Pre-trained Transformer (GPT),which employs the Neighbor-Joining method to construct phylogenetic trees. NJGPT simplifies phylogenetic tree construction by allowing users to generate and visualize trees using natural language queries. It supports multiple sequence file formats, matrix calculation models, and gap-deletion methods. To evaluate the performance of NJGPT, we compared output and runtimes with the widely-used phylogenetic software, MEGA. Our results show that NJGPT produces identical trees over a range of sequence lengths and simple models of evolution. However, NJGPT faces visualization issues with datasets over 50 taxa and operational failures with larger datasets due to token limits. NJGPT runtimes were also substantially slower than MEGA; however, NJGPT’s user-friendly interface makes it ideal for beginners.AvailabilityThis plugin is available for free athttps://chatgpt.com/g/g-1OzP3Qviw-njgpt, the source code is available on GitHub (https://github.com/ZWan622/NJGPT1.0.git) and is implemented using PythonContactzwan622@aucklanduni.ac.nzSupplementary informationSupplementary data are available atBioinformaticsonline.