bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of 111 Pleuronectiformes mitochondrial genomes: insights into structure, conservation, variation and evolution
Authors: Tan Suxu , Wang Wenwen , Li Jinjiang , Sha Zhenxia 
Published: September 2024

AbstractPleuronectiformes, also known as flatfish, are important model and economic animals. However, a comprehensive genome survey of their important organelles, mitochondria, is limited. In this study, we analyzed the genomic structure, codon preference, nucleotide diversity, selective pressure and repeat sequences, as well as reconstructed the phylogenetic relationship using the mitochondrial genomes of 111 flatfish species. Our analysis revealed a conserved gene content of protein-coding genes and rRNA genes, but varying numbers of tRNA genes across species. The mitochondrial genomes of most flatfish were conservative, while obvious gene rearrangements were found in several species, especially for the whole region rearrangement ofnad5-nad6-cytbin Samaridae family and the swapping rearrangement ofnad6andcytbgene in Bothidae family, suggesting a unique evolutionary history or functional benefit. Codon usage showed obvious biases, with adenine being the most frequent nucleotide at the third codon position. Nucleotide diversity and selective pressure analysis suggested that different protein-coding genes underwent varying degrees of evolutionary pressure, withcytbandcoxgenes being the most conserved ones. Phylogenetic analysis using both whole mitogenome information and concatenated independently aligned protein-coding genes largely mirrored the taxonomic classification of the species, with Samaridae family forming a distinct outgroup when the first approach was used. The identification of simple sequence repeats and various long repetitive sequences (forward, reverse, palindromic and complementary repeats) provided additional complexity of genome organization and offered markers for evolutionary studies and breeding practices. In summary, this study represents a significant step forward in our comprehension of the flatfish mitochondrial genomes, providing valuable insights into the structure, conservation and variation within flatfish mitogenomes, with implications for understanding their evolutionary history, functional genomics and fisheries management. Future research can delve deeper into the conservation biology, evolutionary biology and functional usages of variations.
PanCNV-Explorer: A pan-cancer resource to analyze copy number variations
Authors: Kornrumpf Kevin , Dönitz Jürgen 
Published: September 2024

AbstractIntroductionCopy number variations (CNVs) are structural genomic alterations that involve changes in the number of copies of specific DNA regions. These variations can include deletions, duplications, and more complex rearrangements, and play a critical role in cancer progression by amplifying oncogenes, deleting tumor suppressor genes, or altering other key genomic regions. Despite the importance of CNVs in cancer biology, there is a lack of comprehensive resources that aggregate CNV data across multiple cancer types, impeding the exploration of their role in different malignancies. The PanCNV-Explorer was developed to fill this gap by providing a pan-cancer resource that integrates CNV data for over 21 cancer types.MethodsThe PanCNV-Explorer was developed, utilizing data from repositories such as COSMIC, DepMap, DGV, and dbVAR. Amplifications and deletions can be visualized, with detailed chromosome-specific plots highlighting CNV patterns. In addition, a genome browser has been implemented to display regions of interest for searching for genes of potential relevance.ResultsThe database contains over 5 million CNVs from 15,809 samples, spanning 21 primary cancer types. Pathogenic CNVs from ClinVar and DepMap were compared to benign data from DGV and dbVAR, allowing a comprehensive analysis across tissues. CNV patterns were visualized for individual cancers. We demonstrate with use cases, focusing on common oncogenes such as MYC and tumor suppressor genes such as TP53, the ability of the resource to search for cancer driver genes. For example, chromosome 12 in pancreatic cancer showed frequent amplifications in the region containing the KRAS oncogene. In another example, we show how driver gene candidates already described in certain cancer entities can also be found with high frequency in other entities.ConclusionThe PanCNV-Explorer provides a valuable resource for pan-cancer CNV analysis, facilitating the exploration of CNV-driven tumor heterogeneity. The integrated visualization tools and genome browser enable detailed exploration of genomic regions, enhancing cancer research. As a valuable and easy-to-use platform that allows researchers to quantify and compare CNVs across cancer types, the PanCNV-Explorer is an essential tool for advancing cancer genomics research. The main page is available athttps://mtb.bioinf.med.uni-goettingen.de/pancnv-explorer/.
Exploring the role of Large Language Models in Melanoma: a Systemic Review
Authors: Zarfati Mor , Nadkarni Girish N , Glicksberg Benjamin S , Harats Moti , Greenberger Shoshana , Klang Eyal , Soffer Shelly 
Published: September 2024

ABSTRACTBackgroundLarge language models (LLMs) are gaining recognition across various medical fields; however, their specific role in dermatology, particularly in melanoma care, is not well- defined. This systematic review evaluates the current applications, advantages, and challenges associated with the use of LLMs in melanoma care.MethodsWe conducted a systematic search of PubMed and Scopus databases for studies published up to July 23, 2024, focusing on the application of LLMs in melanoma. Identified studies were categorized into three subgroups: patient education, diagnosis and clinical management. The review process adhered to PRISMA guidelines, and the risk of bias was assessed using the modified QUADAS-2 tool.ResultsNine studies met the inclusion criteria. Five studies compared various LLM models, while four focused on ChatGPT. Three studies specifically examined multi-modal LLMs. In the realm of patient education, ChatGPT demonstrated high accuracy, though it often surpassed the recommended readability levels for patient comprehension. In diagnosis applications, multi- modal LLMs like GPT-4V showed capabilities in distinguishing melanoma from benign lesions. However, the diagnostic accuracy varied considerably, influenced by factors such as the quality and diversity of training data, image resolution, and the models’ ability to integrate clinical context. Regarding management advice, one study found that ChatGPT provided more reliable management advice compared to other LLMs, yet all models lacked depth and specificity for individualized decision-making.ConclusionsLLMs, particularly multimodal models, show potential in improving melanoma care through patient education, diagnosis, and management advice. However, current LLM applications require further refinement and validation to confirm their clinical utility. Future studies should explore fine-tuning these models on large dermatological databases and incorporate expert knowledge.
Peroxiredoxin 2 mediates redox-stimulated adaptations to oxidative phosphorylation induced by contractile activity in human skeletal muscle myotubes
Authors: Heaton Robert A , Ball Sam T M , Staunton Caroline A , Mouly Vincent , Jones Samantha W , McArdle Anne , Jackson Malcolm J 
Published: September 2024

AbstractSkeletal muscle generates superoxide during contractions, which is converted to hydrogen peroxide (H2O2). H2O2has been proposed to activate signalling pathways and transcription factors that regulate adaptive responses to exercise, but the concentration required to oxidize and activate key redox-sensitive signalling proteinsin vitrois much higher than the typical intracellular levels seen in muscle after exercise. We hypothesized that 2-Cys-peroxiredoxins (PRDX), which rapidly oxidize in the presence of physiological concentrations of H2O2, serve as intermediary signalling molecules and play a crucial role in activating adaptive pathways following muscle contractions. This study has examined the human muscle myotube responses to contractile activity, or exposure to low extracellular concentrations (2.5-5 µM) of H2O2and whether knock down of muscle PRDX2 alters the differential gene expression (DEG) that results from these stresses. Exposure of human skeletal muscle myotubes to a 15 min period of aerobic electrically stimulated isometric contractions or 5μM H2O2induced substantial changes in DEG with modification of many genes associated with adaptations of skeletal muscle to contractile activity. Common DEG in these conditions included upregulation of genes associated with increased mitochondrial oxidative phosphorylation, includingCOX1, COX2, COX3andATP6. In myotubes with PRDX2 knock down (94% decrease in PRDX2 mRNA), the upregulation of genes associated with increased mitochondrial oxidative phosphorylation was abolished following contractile activity or exposure to H2O2. These data indicate that a common effect of contractile activity and exposure to “physiological” levels of H2O2in human myotubes is to increase the expression of multiple genes associated with increased mitochondrial oxidative phosphorylation. Furthermore, these effects were abolished in PRDX2 knock down myotubes indicating that adaptations to upregulate multiple genes related to increased mitochondrial capacity in human muscle myotubes in response to exercise is both redox regulated and requires PRDX2 as an essential mediator of the effects of H2O2.
Genome biology of long non-coding RNAs in humans: a virtual karyotype
Authors: Palma Alessandro , Buonaiuto Giulia , Ballarino Monica , Laneve Pietro 
Published: September 2024

AbstractBackgroundLong non-coding RNAs (lncRNAs) represent a unique and groundbreaking class of RNA molecules that exert regulatory functions with remarkable tissue and cellular specificities. Although the number of identified functional lncRNAs is increasing, comprehensive profiling of lncRNA genomics remains elusive. Creating a virtual lncRNA karyotype is especially important for species whose intrinsic features enable their biosynthesis and function in context-dependent manners.Results and conclusionsTo address this challenge, we employed existing annotation files to create a statistical genomics portrait of lncRNA genes for comparison with protein-coding genes. We provide a foundational reference for exploring the non-coding genome, offering insights into the genomic characteristics of lncRNAs that may enhance understanding of their biological significance and impact.
Elavl1 is dispensable for appendicular skeletal development
Authors: Parsha Rohini , Kota Satya K. 
Published: September 2024

AbstractElavl1/HuR is a RNA binding protein implicated in multiple developmental processes with pleiotropic roles in RNA life cycle. Loss of Elavl1 is incompatible with life with early embryonic loss of Elavl1 in epiblast cells being lethal with defects in placental branching and embryonic tissue growth. Postnatal global deletion of Elavl1/HuR results in lethality with atrophy in multiple tissues mainly due to loss of progenitor cells. However, roles of Elavl1 specifically during embryonic limb development is not well understood. Here we report that deletion of Elavl1 in limb bud mesenchyme in mouse did not reveal any abnormalities during embryonic development with normal development in pre- and postnatal limb skeleton. Analyses of skeletal patterning, morphogenesis and skeletal maturation including skeletal elements in stylopod, zeugopod and autopod during development did not reveal any significant differences between long bones from control and Elavl1 conditional knockout animals. Our study indicates differential dependency and susceptibility to loss of Elavl1 in different stem cell lineages with its functions being dispensable during limb development.
Metabolic mapping of the human solute carrier superfamily
Authors: Wiedmer Tabea , Teoh Shao Thing , Christodoulaki Eirini , Wolf Gernot , Tian Chengzhe , Sedlyarov Vitaly , Jarret Abigail , Leippe Philipp , Frommelt Fabian , Ingles-Prieto Alvaro , Lindinger Sabrina , Barbosa Barbara M. G. , Onstein Svenja , Klimek Christoph , Garcia Julio , Serrano Iciar , Reil Daniela , Santacruz Diana , Piotrowski Mary , Noell Stephen , Bueschl Christoph , Li Huanyu , Chi Gamma , Mereiter Stefan , Oliveira Tiago , Penninger Josef M. , Sauer David B. , Steppan Claire M. , Viollet Coralie , Klavins Kristaps , Hannich J. Thomas , Goldmann Ulrich , Superti-Furga Giulio 
Published: September 2024

AbstractSolute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked to cellular function and identity. Despite their key role, individual functions of the members of the SLC superfamily were not evaluated systematically. We determined the metabolic and transcriptional profiles upon SLC overexpression in knock-out or wild-type isogenic cell backgrounds. Targeted metabolomics provided a fingerprint of 189 intracellular metabolites, while transcriptomics offered insights into cellular programs modulated by SLC expression. Beyond the metabolic profiles of 102 SLCs directly related to their known substrates, we also identified putative substrates or metabolic pathway connections for 71 SLCs without previously annotatedbona fidesubstrates, including SLC45A4 as a new polyamine transporter. By comparing the molecular profiles, we identified functionally related SLC groups, including some with distinct impacts on osmolyte balancing and glycosylation. The assessment of functionally related human genes presented here may serve as a blueprint for other systematic studies of human gene function and supports future investigations into the functional roles of SLCs.
Single-cell multi-omic analysis reveals principles of transcription-chromatin interaction during embryogenesis
Authors: Bhardwaj Vivek , Griffa Alberto , Gaza Helena Viñas , Zeller Peter , van Oudenaarden Alexander 
Published: September 2024

AbstractEstablishing a cell-type-specific chromatin landscape is critical for the maintenance of cell identity during embryonic development. However, our knowledge of how this landscape is set during vertebrate embryogenesis has been limited, due to the lack of methods to jointly detect chromatin modifications and gene expression in the same cell. Here we present a multimodal measurement of full-length transcriptome and chromatin modifications in individual cells during early embryonic development in zebrafish. We show that before the formation of germ layers, the chromatin and transcription states of cells are uncoupled, and become progressively connected during gastrulation and somitogenesis. Silencing of key developmental genes is achieved by local spreading of repressive chromatin as development proceeds. We use a joint analysis of transcription factor (TF) expression and chromatin states to predict lineage-specific activators and repressors and identify a subset of TFs that are themselves epigenetically regulated. Altogether, our data resolves the dynamic relationship between chromatin and transcription during early embryonic development and clarifies how these two layers interact to establish cell identity.
A stolen future – aberrant hippocampal neurogenesis produces glial cells in epilepsy
Authors: Toby Segasby , Roozbeh Sanaei , Natalija Aleksejenko , Omar Mamad , David Henshall , Achilleas Floudas , Janosch Heller 
Published: September 2024

AbstractAdult hippocampal neurogenesis is disturbed in epilepsy. The increased neuronal activity in the epileptic brain leads to an increased production of newborn cells, increased mossy fibre sprouting and altered integration of new neurons within the hippocampus. Here, we set out to investigate increased astrocyte numbers following status epilepticus. We used immunolabelling of brain sections from the mouse intra-amygdala kainic acid model of epilepsy and publicly available single cell RNA sequencing datasets to assess newborn cells in the dentate gyrus. Similar to published series we found on increased number of reactive astrocytes present in the epileptic hippocampus. Additionally, we identified a cell population that expressed neurogenesis (doublecortin) and astrocyte (glial fibrillary acidic protein) markers in the epileptic brain, both in mouse and in human tissue. We further evaluated the expression profile of these cells. Immunolabelling showed expression of mature astrocyte markers aquaporin 4 and glutamate transporter-1. The single cell RNA sequencing data highlighted expression of neurogenesis and astrocyte markers in the doublecortin/glial fibrillary acidic protein-expressing cells. In conclusion, epilepsy pushes early neuroblasts to fate-switch to an astrocyte lineage as seen in the kainic acid-induced mouse model and in human resected brain tissue. Further understanding how neurogenesis is altered in epilepsy and whether the neuroblast fate-switch can be reverted will help in finding novel therapy strategies for epilepsy and other neurological diseases associated with aberrant adult hippocampal neurogenesis.Key MessagesFollowing kainic acid-induced status epilepticus early neuroblasts appear to undergo a fate-switch to an astrocyte lineage. We were able to confirm the presence of cells positive for early neurogenesis and astrocyte markers in human epileptic tissue using scRNAseq data.
From Genes to Pathways: A Curated Gene Approach to Accurate Pathway Reconstruction in Teleost Fish Transcriptomics
Authors: Herrera Marcela , Vianello Stefano , Mitchell Laurie , Chamot Zoé , Lorin-Nebel Catherine , Roux Natacha , Besseau Laurence , Gibert Yann , Laudet Vincent 
Published: September 2024

AbstractInterpreting the vast amounts of data generated by high-throughput sequencing technologies can often present a significant challenge, particularly for non-model organism. While automated approaches like GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses are widely used, they often lack specificity for non-model organisms. To bridge this gap, we present a manually curated gene list tailored for teleost fish transcriptomics. This resource focuses on key biological processes crucial for understanding teleost fish physiology, development, and adaptation, including hormone signaling, various metabolic pathways, appetite regulation, digestion, gastrointestinal function, vision, ossification, osmoregulation, and pigmentation. Developed through collaborative efforts of specialists in diverse fields, the list prioritizes genes with established roles in teleost physiology, experimental evidence, and conservation across species. This curated list aims to provide researchers with a reliable starting point for transcriptomic analyses, offering a carefully evaluated set of genes relevant to current research priorities. By streamlining the process of gene selection and interpretation, this resource supports the broader teleost fish research community in designing and analyzing studies that investigate molecular responses to developmental and environmental changes. We encourage the scientific community to collaboratively expand and refine this list, ensuring its continued relevance and utility for teleost fish research.
Ancient biomolecules suggest learned foraging strategy in extinct cave bears
Authors: Meleg Ioana N. , Alberti Federica , Drucker Dorothée G. , Năpăruş-Aljancic Magdalena , Feurdean Angelica , Robu Marius , Vlaicu Marius , Naito Yuichi I. , Boroneanț Adina , Cârciumaru Marin , Nițu Elena C. , Hofreiter Michael , Bocherens Hervé , Barlow Axel 
Published: September 2024

AbstractStudying the behavioural ecology of long-extinct species is challenging due to the difficulty in measuring the behavioural phenotype and correlating this with genetic and environmental factors. However, a multidisciplinary approach integrating isotope analysis of diet and ancient DNA analysis of genetic relationships offers a potential framework to test the proximate causes of dietary preferences. Our study focuses on Late Pleistocene cave bears from the Romanian Carpathians. Stable isotope analysis of bone collagen reveals substantial lifetime variation in food plant preferences among individuals. We find that bears with similar diets do not cluster according to their population structure, sex, time period, climatic conditions, or location. This disconnect suggests that diet preference in cave bears is not genetically inherited, and instead that individuals adapted their diets based on foraging experience. This integrative approach opens new avenues for understanding Pleistocene animal behaviour, leveraging ancient biomolecules synergistically to reveal insights otherwise inaccessible.
Design of an intracellular aptamer-based fluorescent biosensor to track burden in E. coli
Authors: Grob Alice , Copeman Tom , Chen Sifeng , Elani Yuval , Franco Elisa , Ceroni Francesca 
Published: September 2024

AbstractCell burden impacts the performance of engineered synthetic systems. For this reason, there is great interest toward the development of tools to track burden and improve biotechnology applications. Fluorogenic RNA aptamers are excellent candidates for live monitoring of burden because their production is expected to impose a negligible load on transcription resources. Here we characterise the performance of a library of aptamers when expressed from different promoters inE. coli. We find that aptamer relative performance is dependent on the promoter and the strain, and that, contrary to expectation, aptamer expression impacts host fitness. By selecting two of the aptamers with brighter output and lower impact, we then design an intracellular biosensor able to report on the activation of the burden response in engineered cells. The sensor developed here adds to the collection of tools available for burden mitigation and may support bioprocessing applications where improved host performance is sought.
Pleiotrophin deletion prevents high-fat diet-induced cognitive impairment, glial responses, and alterations of the perineuronal nets in the hippocampus
Authors: Cañeque-Rufo Héctor , Fontán-Baselga Teresa , Galán-Llario Milagros , Zuccaro Agata , Sánchez-Alonso María Gracia , Gramage Esther , del Pilar Ramos-Álvarez María , Herradón Gonzalo 
Published: September 2024

ABSTRACTObesity and metabolic disorders, such as metabolic syndrome (MetS) facilitate the development of neurodegenerative diseases and cognitive decline. Persistent neuroinflammation plays an important role in this process. Pleiotrophin (PTN) is a cytokine that regulates energy metabolism and high-fat diet (HFD)-induced neuroinflammation, suggesting that PTN could play an important role in the connection between obesity and brain alterations, including cognitive decline. To test this hypothesis, we used an HFD-induced obesity model inPtngenetically deficient mice (Ptn−/−). First, we confirmed thatPtndeletion prevents HFD-induced obesity. Our findings demonstrate that feeding wild-type (Ptn+/+) mice with HFD for 6 months results in short- and long-term memory loss in the novel object recognition task. Surprisingly, we did not observe any sign of cognitive impairment inPtn−/−mice fed with HFD. In addition, we observed that HFD induced microglial responses, astrocyte depletion, and perineuronal nets (PNNs) alterations inPtn+/+mice, while these effects of HFD were mostly prevented inPtn−/−mice. These results show a crucial role of PTN in metabolic responses and brain alterations induced by HFD and suggest the PTN signalling pathway as a promising therapeutic target for brain disorders associated with MetS.