bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitotic transcription ensures ecDNA inheritance through chromosomal tethering
Authors: Nichols Ashley , Norman Roshan , Chen Yanyang , Choi Yujin , Striepen Josefine , Salataj Eralda , Toufektchan Eleonore , Koche Richard , Maciejowski John 
Published: February 2025

SUMMARYExtrachromosomal DNA (ecDNA) are circular DNA bodies that play critical roles in tumor progression and treatment resistance by amplifying oncogenes across a wide range of cancer types. ecDNA lack centromeres and are thus not constrained by typical Mendelian segregation, enabling their unequal accumulation within daughter cells and associated increases in copy number. Despite intrinsic links to their oncogenic potential, the fidelity and mechanisms of ecDNA inheritance are poorly understood. Here, we show that ecDNA are protected against cytosolic mis-segregation through mitotic clustering and by tethering to the telomeric and subtelomeric regions of mitotic chromosomes. ecDNA-chromosome tethering depends on BRD4 transcriptional co-activation and mitotic transcription of the long non-coding RNAPVT1, which is co-amplified withMYCin colorectal and prostate cancer cell lines. Disruption of ecDNA-chromosome tethering through BRD4 inhibition,PVT1depletion, or inhibiting mitotic transcription results in cytosolic mis-segregation, ecDNA reintegration, and the formation of homogeneously staining regions (HSRs). We propose that nuclear inheritance of ecDNA is facilitated by an RNA-mediated physical tether that links ecDNA to mitotic chromosomes and thus protects against cytosolic mis-segregation and chromosomal integration.
Morpheus: A fragment-based algorithm to predict metamorphic behaviour in proteins across proteomes
Authors: Subramanian Vijay , Appadurai Rajeswari , Venkatesh Harikrishnan , Sekhar Ashok , Srivastava Anand 
Published: February 2025

AbstractFunctionally important “fold-switching” proteins, which do not obey the classical folding dogma, are now thought to be widespread. Algorithms that can accurately annotate fold-switching proteins from sequence information can help uncover the true extent of the “metamorphome”. Here, we present Morpheus, a fragment-based classification approach, that works by analysing the diversity of structures within a query protein sequence. Morpheus exhaustively curates and uses fragment structural data from the protein data bank as well as the AlphaFold Protein Structure Database. We employed our algorithm on 57 different proteomes consisting of a total of 601,218 proteins and identified about 10% of these proteins with the ability to fold switch. Additionally, we provide a web server for Morpheus to test for metamorphic propensities for user-defined sequences (http://mbu.iisc.ac.in/∼anand/morpheus). Besides screening for metamorphic behaviour in proteomes, our work will be useful in de novo design and engineering of such proteins through further experimentation.
Investigation of mitochondrial phenotypes in motor neurons derived by direct conversion of fibroblasts from familial ALS subjects
Authors: Woo Evan , Tasnim Faiza , Kawamata Hibiki , Manfredi Giovanni , Konrad Csaba 
Published: February 2025

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, leading to fatal muscle paralysis. Familial forms of ALS (fALS) account for approximately 10% of cases and are associated with mutations in numerous genes. Alterations of mitochondrial functions have been proposed to contribute to disease pathogenesis. Here, we employed a direct conversion (DC) technique to generate induced motor neurons (iMN) from skin fibroblasts to investigate mitochondrial phenotypes in a patient-derived disease relevant cell culture system. We converted 7 control fibroblast lines and 17 lines harboring the following fALS mutations, SOD1A4V, TDP-43N352S, FUSR521G, CHCHD10R15L, and C9orf72 repeat expansion. We developed new machine learning approaches to identify iMN, analyze their mitochondrial function, and follow their fate longitudinally. Mitochondrial and energetic abnormalities were observed, but not all fALS iMN lines exhibited the same alterations. SOD1A4V, C9orf72, and TDP-43N352SiMN had increased mitochondrial membrane potential, while in CHCHD10R15Lcells membrane potential was decreased. TDP-43N352SiMN displayed changes in mitochondrial morphology and increased motility. SOD1A4V, TDP-43N352S, and CHCHD10R15LiMN had increased oxygen consumption rates and altered extracellular acidification rates, reflecting a hypermetabolic state similar to the one described in sporadic ALS fibroblasts. FUSR521Gmutants had decreased ATP/ADP ratio, suggesting impaired energy metabolism. We then tested the viability of iMN and found decreases in survival in SOD1A4V, C9orf72, and FUSR521G, which were corrected by small molecules that target mitochondrial stress. Together, our findings reinforce the role of mitochondrial dysfunction in ALS and indicate that fibroblast-derived iMN may be useful to study fALS metabolic alterations. Strengths of the DC iMN approach include low cost, speed of transformation, and the preservation of epigenetic modifications. However, further refinement of the fibroblasts DC iMN technique is still needed to improve transformation efficiency, reproducibility, the relatively short lifespan of iMN, and the senescence of the parental fibroblasts.
Odd-chain dicarboxylic acid feeding recapitulates the biochemical phenotype of glutaric aciduria type 1 in mice
Authors: Richert Adam C. , Zhang Yuxun , Bharathi Sivakama S. , Hernandez Abigail , Dodatko Tetyana , Bons Joanna , Stauffer Brandon , Yu Chunli , Schilling Birgit , Houten Sander M. , Goetzman Eric S. 
Published: February 2025

ABSTRACTGlutaric aciduria type-1 (GA1) is an inherited mitochondrial neurometabolic disorder with a poorly understood pathogenesis and unmet medical needs. GA1 can be diagnosed via its hallmark biochemical signature consisting of glutaric aciduria, 3-hydroxyglutaric aciduria, and increased plasma glutarylcarnitine. These glutaryl-CoA-derived metabolites are thought to originate solely in the mitochondria. Here, we demonstrate that wild-type mice fed an 11-carbon odd-chain dicarboxylic acid (undecanedioic acid, DC11) recreates the biochemical phenotype of GA1. Odd-chain dicarboxylic acids like DC11are not present in food but can arise from several endogenous processes, such as lipid peroxidation and fatty acid ω-oxidation. DC11is chain-shortened in peroxisomes to glutaryl (DC5)-CoA, which then gives rise to the GA1-like pattern of DC5metabolites in urine, tissues, and blood. Glutaric acid released from peroxisomes during DC11chain-shortening can enter mitochondria, be activated to CoA by the enzyme succinyl-CoA:glutarate-CoA transferase (SUGCT), and become substrate for glutaryl-CoA dehydrogenase (GCDH), the enzyme that is mutated in GA1. Our data provide proof-of-concept that the generation of dicarboxylic acids by ω-oxidation, which is stimulated during the same catabolic states known to trigger acute encephalopathy in GA1, may exacerbate disease by increasing the glutaryl-CoA substrate load in mitochondria.
Comparative analysis of macrophage feeder systems reveals distinct behaviors and key transcriptional shifts in chronic lymphocytic leukemia cells via coculture
Authors: Kohlhas Viktoria , Jestrabek Hendrik , Rebollido-Rios Rocio , Truong Thanh Tung , Zölzer Rebekka , Schreurs Luca D. , von Lom Anton , vom Stein Alexander F. , Hallek Michael , Nguyen Phuong-Hien 
Published: February 2025

AbstractIn this brief report, we evaluated various macrophage coculture systems for their CLL-feeding potential, phagocytosis capacity, induction of treatment resistance in CLL cells, and their impact on the transcriptional profiles of CLL cells.
Phylogenomics ofMessorharvester ants (Hymenoptera: Formicidae: Stenammini) unravels their biogeographical origin and diversification patterns
Authors: Juvé Yannick , Weyna Arthur , Lauroua Elodie , Nidelet Sabine , Khaldi Mourad , Barech Ghania , Lebas Claude , Rasplus Jean-Yves , Cruaud Astrid , Condamine Fabien L. , Romiguier Jonathan 
Published: February 2025

AbstractAs a major abiotic factor, climate change is expected to profoundly alter biological communities. On this basis, identifying how past temperature variations affected species diversification and distribution can help to predict the effects of the ongoing climate change. In this study, we focused on the harvester ant genusMessorwhich is mostly adapted to dry environments dominated by seed-producing plants. The phylogenetic analysis of 2,524 markers obtained from 58Messorspecies/subspecies, supports their emergence in the Irano-Indian area approximately 20 Mya. Phylogenetic relationships uncovered in this study enabled us to redefine historical taxonomic groups, providing a solid basis for future revisions that encompass the entire genus diversity. Their diversification appears to be affected by temperature, with a higher speciation rate during warmer periods. This confirms that the ecological specialization ofMessormakes them strongly dependent on thermal conditions. Our results highlight the importance of abiotic factors on diversification processes, especially for highly specialized species that may exhibit predictable evolutionary responses to climate changes.
Reproductive Adaptation ofAstyanax mexicanusUnder Nutrient Limitation
Authors: Xia Fanning , Santacruz Ana , Wu Di , Bertho Sylvain , Fritz Elizabeth , Morales-Sosa Pedro , McKinney Sean , Nowotarski Stephanie H. , Rohner Nicolas 
Published: February 2025

AbstractReproduction is a fundamental biological process for the survival and continuity of species. Examining changes in reproductive strategies offers valuable insights into how animals have adapted their life histories to different environments. Since reproduction is one of the most energy-intensive processes in female animals, nutrient scarcity is expected to interfere with the ability to invest in gametes. Lately, a new model to study adaptation to nutrient limitation has emerged; the Mexican tetraAstyanax mexicanus. This fish species exists as two different morphs, a surface river morph and a cave-dwelling morph. The cave-dwelling morph has adapted to the dark, biodiversity, and nutrient-limited cave environment and consequently evolved an impressive starvation resistance. However, how reproductive strategies have adapted to nutrient limitations in this species remains poorly understood. Here, we compared breeding activities and maternal contributions between laboratory-raised surface fish and cavefish. We found that cavefish produce different clutch sizes of eggs with larger yolk compared to surface fish, indicating a greater maternal nutrient deposition in cavefish embryos. To systematically characterize yolk compositions, we used untargeted proteomics and lipidomics approaches to analyze protein and lipid profiles in 2-cell stage embryos and found an increased proportion of sphingolipids in cavefish compared to surface fish. Additionally, we generated transcriptomic profiles of surface fish and cavefish ovaries using a combination of single cell and bulk RNA sequencing to examine differences in maternal contribution. We found that genes essential for hormone regulation were upregulated in cavefish follicular somatic cells compared to surface fish. To evaluate whether these differences contribute to their reproductive abilities under natural-occurring stress, we induced breeding in starved female fish. Remarkably, cavefish maintained their ability to breed under starvation, whereas surface fish largely lost this ability. We identifiedinsulin-like growth factor 1a receptor(igf1ra) as a potential candidate gene mediating the downregulation of ovarian development genes, potentially contributing to the starvation-resistant fertility of cavefish. Taken together, we investigated the female reproductive strategies inAstyanax mexicanus, which will provide fundamental insights into the adaptations of animals to environments with extreme nutrient deficit.
Shared Lineage, Distinct Outcomes: Yap and Taz Loss Differentially Impact Schwann and Olfactory Ensheathing Cell Development Without Disrupting GnRH-1 Migration
Authors: Taroc Ed Zandro M. , Amato Enrico , Semon Alexis , Dolphin Nikki , Beck Briane , Belin Sophie , Poitelon Yannick , Forni Paolo E. 
Published: February 2025

AbstractOlfactory Ensheathing Cells (OECs) are glial cells originating from the neural crest, critical for bundling olfactory axons to the brain. Their development is crucial for the migration of Gonadotropin-Releasing Hormone-1 (GnRH-1) neurons, which are essential for puberty and fertility. OECs have garnered interest as potential therapeutic targets for central nervous system lesions, although their development is not fully understood.Our single-cell RNA sequencing of mouse embryonic nasal tissues suggests that OECs and Schwann cells share a common origin from Schwann cell precursors yet exhibit significant genetic differences. The transcription factors Yap and Taz have previously been shown to play a crucial role in Schwann cell development. We usedSox10-Cre mice to conditionally ablateYapandTazin migrating the neural crest and its derivatives. Our analyses showed reduced Sox10+ glial cells along nerves in the nasal region, altered gene expression of SCs, melanocytes, and OECs, and a significant reduction in olfactory sensory neurons and vascularization in the vomeronasal organ. However, despite these changes, GnRH-1 neuronal migration remained unaffected.Our findings highlight the importance of the Hippo pathway in OEC development and how changes in cranial neural crest derivatives indirectly impact the development of olfactory epithelia.
Using a Novel-Liaison Based Social Media Intervention Utilizing Community Feedback to Improve Organizational Health Literacy in Covid-19 Crisis Communication
Authors: Matangi Nishita , Granillo Cristie , Joachim-Célestin Maud , Fuentes Karla Estudillo , Irani Crissy , Thiruvengadam Nikhil , Montgomery N Susanne 
Published: February 2025

AbstractThe COVID-19 pandemic exposed historical pervasive gaps in information and resources for vulnerable communities. In an academic community partnered response of a consortium of already collaborating community and academic partners, the COVID Care Corps (CCC), was developed to create and disseminate public health information to individuals in the Inland Empire (IE) by including community liaisons to implement a systematic feedback loop to assure community voice. Liaisons made disseminating information and getting community feedback more efficiently in a time of crisis when information needed to be immediate. As a result, it was found that although community was concerned about the pandemic, they also wanted information about other social determinants of health (immigration, finances, housing and job security= often presented as competing priorities to the pandemic. This resulted in a shift in content creation to aligned with community needs and interests. Establishing trust through community relationships and identifying community liaisons should be implemented prior to a crisis to ensure the quick dissemination of information needed for local buy-in and true equitable health communication.
Microbial ecology of acidic, biogenic gypsum: Community structure and distribution of extremophiles on freshly formed and relict sulfate deposits in a hydrogen sulfide-rich cave
Authors: Havlena Zoë E. , Lucero Katherine , Graham Heather V. , Stern Jennifer C. , Wankel Scott D. , Mainiero Maurizio , Jones Daniel S. 
Published: February 2025

AbstractSulfate minerals are abundant on the Martian surface, and many of these evaporite deposits are thought to have precipitated from acidic fluids. On Earth, gypsum (CaSO4•2H2O) and other sulfates sometimes form under acidic conditions, so exploring the extremophilic life that occurs in these mineral environments can help us evaluate the astrobiological potential of acid sulfate depositional settings. Here, we characterized the microbial communities associated with acidic gypsum deposits in a sulfuric acid cave, where sulfate precipitation is driven by sulfide-oxidizing bacteria and archaea. We used 16S rRNA gene sequencing and cell counts to characterize gypsum-associated microorganisms in freshly formed and relict deposits throughout the cave, in order to test hypotheses about how microbial community composition and abundance would vary with distance from the sulfidic water table and with the concentration of H2S(g) and other gases in the cave atmosphere. We found that actively-forming gypsum in the lower cave levels was colonized by low diversity communities of sulfide-oxidizing chemolithotrophs and other acidophiles that have few cells compared to other environments in the cave. The most abundant taxa wereAcidithiobacillus, Metallibacterium, Mycobacteria, and three differentThermoplasmatales-group archaea, which occupied distinct niches based on proximity to sulfidic streams and the concentration of gases in the cave air. In contrast, deposits in older cave levels had more diverse communities that are dominated by chemoorganotrophic and methanotrophic taxa. These findings show that acidic sulfate deposits serve as habitats for extremophilic microorganisms, and broaden our knowledge of the life associated with terrestrial sulfates.ImportanceGypsum and other sulfate salts are common on Mars, and many of these deposits are thought to have formed from acidic fluids early in the planet’s history. Understanding the life that survives and thrives in similar environments on Earth is therefore crucial for evaluating whether these Martian sulfates are or ever were habitable. One such environment where acidic gypsum occurs is in sulfuric acid caves, where extremophilic microorganisms drive the precipitation of sulfate minerals by oxidizing hydrogen sulfide gas from the cave atmosphere. Here, we characterized the communities of microorganisms on freshly formed and ancient gypsum in the Frasassi Caves, and found that the gypsum deposits hosted microbial communities that changed based on chemical energy availability and the age of the gypsum. Our findings underscore the importance of chemical and microbiological interactions in shaping habitable niches, and provide context for searching for past or present life in acidic Martian sulfates.
Rostro-caudal TMS mapping of immediate transcranial evoked potentials reveals a pericentral crescendo-decrescendo pattern
Authors: Nuyts Marten , Beck Mikkel Malling , Banach Agata , Thielscher Axel , Meesen Raf , Tomasevic Leo , Siebner Hartwig Roman , Christiansen Lasse 
Published: February 2025

AbstractBackgroundWe recently demonstrated that single-pulse TMS of the primary sensorimotor hand area (SM1HAND) elicits an immediate transcranial evoked potential (iTEP). This iTEP response appears within 2–7 ms post-TMS, featuring high-frequency peaks superimposed on a slow positive wave. Here, we used a linear TMS-EEG mapping approach to characterize the rostro-caudal iTEP expression and compared it to that of motor-evoked potentials (MEPs).MethodsIn 15 healthy young volunteers (9 females), we identified the iTEP hotspot in left SM1HAND. We applied single biphasic TMS pulses at an intensity of 110% of resting motor threshold over six cortical sites along a rostro-caudal axis (2 cm rostral to 3 cm caudal to the SM1HANDhotspot). We analyzed site-specific iTEP and MEP responses.ResultsiTEP magnitude decreased rostrally and caudally from the SM1HANDhotspot. MEPs exhibited a similar rostro-caudal crescendo-decrescendo pattern. While iTEP and MEP response profiles were similar, normalized iTEP amplitudes decayed less rapidly at the first postcentral site.DiscussionThese findings support the idea that pericentral iTEPs reflect a direct response signature of the pericentral cortex, possibly involving a synchronized TMS-induced excitation of cortical pyramidal tract neurons. Similar but non-identical rostro-caudal patterns suggest that iTEPs and MEPs may arise from overlapping but distinct neuronal populations.
Biochemical properties of glycerol kinase from the hypersaline-adapted archaeonHaloferax volcanii
Authors: Sanchez Karol M. , Maupin-Furlow Julie A. 
Published: February 2025

ABSTRACTExtremophilic microorganisms hold promise to serve as robust biocatalysts in the conversion of glycerol waste into high value products.Haloferax volcaniiis a hypersaline-adapted archaeon that prefers glycerol over glucose and channels this carbon source into central metabolism through glycerol kinase (GK). Here we report the biochemical properties of theH. volcaniiGK and evaluated its potential for biotechnological applications. The N-terminal His-tagged form of GK was found functionalin vivoand was readily purified to homogeneity at 4.5-fold higher yield (3 mg/L culture) than GK fused to a C-terminal StrepII tag. Further analysis of His-GK by size exclusion chromatography revealed the enzyme exhibited a glycerol-induced shift from a homodimer to a homodimer-homotetramer equilibrium. Purified His-GK demonstrated robust activity over a broad pH and salinity range, with optimal activity at 100 mM NaCl and 50-60 °C. The enzyme was catalytically active in organic solvent (5-10 % DMSO) and crude glycerol containing methanol. His-GK was also found to exhibit full activity after freeze-thaw, showed prolonged thermotolerance in 2 M NaCl supplemented buffers, and had a melting temperature (Tm) in the range of 83-84 °C. Kinetic analysis using the Hill equation indicated His-GK displayed positive cooperativity for glycerol, ATP, and magnesium, with manganese and cobalt also found to serve as divalent cation cofactors. These findings underscore the unique and robust enzymatic properties ofH. volcaniiGK, representing the first known GK to exhibit positive cooperativity with glycerol and ATP, and highlighting its potential for biotechnological applications in glycerol conversion.IMPORTANCEThis study provides new insight into glycerol kinase kinetics through the discovery of an enzyme exhibiting positive cooperativity for glycerol and ATP. By purifying and characterizingH. volcaniiglycerol kinase, this work marks the first isolation of a glycerol kinase from a halophilic archaeon. The enzyme displays unique properties, including resilience to organic solvents, high temperatures, and extreme salinity. It also exhibits sigmoidal kinetics, with Hill coefficients averaging n = 2 for glycerol, ATP, and magnesium, indicating positive cooperativity. This behavior, previously unobserved in other glycerol kinases, aligns with the preference ofH. volcaniifor glycerol over glucose. Given the role of glycerol kinases in converting glycerol waste into value-added products, their efficiency is often a bottleneck in bacterial systems that prefer glucose and struggle under extreme conditions. The distinctive properties ofH. volcaniiglycerol kinase suggest potential for biotechnological applications in harsh environments.
On inputs to deep learning for RNA 3D structure prediction
Authors: Szikszai Marcell , Magnus Marcin , Kadyan Sachin , Rivas Elena 
Published: February 2025

AbstractToday, there are several effective deep learning models for predicting the 3D structure of proteins. Building on their success, models have been developed for predicting the 3D structure of non-coding RNAs. Unfortunately, these models are much less accurate than their protein counterparts. In this paper, we highlight differences between protein and RNA structure, and demonstrate methods for deep learning targeted at addressing those differences, with the aim of prompting discussion on these topics. We present an RNA-specific pipeline for generating structural Multiple Sequence Alignments (MSAs). Derived from the structural alignments, we introduce engineered evolutionary features that strongly inform RNA structure. Further, from the crystal structure, we derive structural features describing RNA base pairing. These evolutionary and structural features can be used in loss functions at different stages of training. Finally, we discuss different cropping strategies informed by RNA structure.