bluuebunny/crossref_metadata_2025_split huggingface dataset:
LIET Model: Capturing the kinetics of RNA polymerase from loading to termination
Authors: Stanley Jacob T. , Barone Georgia E.F. , Townsend Hope A. , Sigauke Rutendo F. , Allen Mary A. , Dowell Robin D. 
Published: October 2024

AbstractTranscription by RNA polymerases is an exquisitely regulated step of the central dogma. Transcription is the primary determinant of cell-state, and most cellular perturbations impact transcription by altering polymerase activity. Thus, detecting changes in polymerase activity yields insight into most cellular processes. Nascent run-on sequencing provides a direct readout of polymerase activity, but no tools exist to model this activity at genes. We focus on RNA polymerase II—responsible for transcribing protein-coding genes. We present the first model to capture the complete process of gene transcription. For individual genes, this model parameterizes each distinct stage of transcription—Loading, Initiation, Elongation, andTermination, hence LIET—in a biologically interpretable Bayesian mixture, which is applied to nascent run-on data. Our improved modeling ofLoading/Initiationdemonstrates these are characteristically different between sense and antisense strands. Applying LIET to 24 human cell-types, our analysis indicates the position of dissociation (the last step ofTermination) appears to be highly consistent, indicative of a highly regulated process. Furthermore, applying LIET to perturbation experiments, we demonstrate its ability to detect specific changes in pausing (5′end), strand-bias, and dissociation location (3′end)—opening the door to differential assessment of transcription at individual stages of individual genes.
Simultaneous Measurement of Gross Oxygen Evolution and Underlying Photosynthetic Redox Reactions: A Case Study Using Cyanobacteria
Authors: Liran Oded 
Published: October 2024

AbstractIn phytoplankton, the intricate balance between respiration and photosynthesis is co-regulated to ensure efficient energy management and adaptation to varying environmental conditions. In cyanobacteria, both processes occur on the same membrane, sharing electron transport carriers within the same cellular compartment. By studying the interaction between photosynthesis and respiration, we can better understand how cyanobacteria balance their energetic budget for survival. In this study, we present an integrated approach that combines tracking gas exchange between cyanobacteria and their environment with analysing the redox kinetics of the underlying photosynthetic electron transport chain. This combined system allows for real-time, simultaneous acquisition of respiration and photosynthesis data. For example, it enabled us to show that the electron transport rate generated by photosystem II, translated toin-vivooxygen concentration, equals the actual concentration of oxygen produced by water splitting plus the amount of oxygen respired. We further demonstrate that our system can accurately assess light respiration in wild-type strains of cyanobacteria, which amounts to 1/10 of their photosynthetic activity under optimal growth conditions. This level of accuracy was previously achievable only with specific cyanobacteria mutants. We envision applying this system in monitoring programs to elaborate on the role of photosynthetic light reactions within the broader context of primary productivity and to understand its dynamics in response to fluctuations in external environmental conditions.
Elevated NAD+drives Sir2A-mediated GCβ deacetylation and OES localization forPlasmodiumookinete gliding and mosquito infection
Authors: Shi Yang , Wan Lin , Jiao Mengmeng , Zhong Chuan-qi , Cui Huiting , Yuan Jing 
Published: October 2024

AbstractcGMP signal-activated ookinete gliding is essential for mosquito midgut infection ofPlasmodiumin malaria transmission. During ookinete development, cGMP synthesizer GCβ polarizes to a unique localization <ookinete extrados site= (OES) until ookinete maturation and activates cGMP signaling for initiating parasite motility. However, the mechanism underlying GCβ translocation from cytosol to OES remains elusive. Here, we used protein proximity labeling to search the GCβ-interacting proteins in ookinetes of the rodent malaria parasiteP. yoelii, and found the top hit Sir2A, a NAD+-dependent sirtuin family deacetylase. Sir2A interacts with GCβ throughout ookinete development. In mature ookinetes, Sir2A co-localizes with GCβ at OES in a mutually dependent manner. Parasites lacking Sir2A lose GCβ localization at OES, ookinete gliding, and mosquito infection, phenocopying GCβ deficiency. GCβ is acetylated at gametocytes but is deacetylated by Sir2A for OES localization at mature ookinetes. We further demonstrated that the level of NAD+, an essential co-substrate for sirtuin, increases during the ookinete development. The NAD+at its maximal level until ookinete maturation promotes Sir2A-catalyzed GCβ deacetylation, ensuring GCβ localization at OES. This study highlights the spatiotemporal coordination of cytosolic NAD+level and NAD+-dependent Sir2A in regulating GCβ deacetylation and dynamic localization forPlasmodiumookinete gliding.
Molecular characterization of the permanent outer-inner membrane contact site of the mitochondrial genome segregation complex in trypanosomes
Authors: Stettler Philip , Schimanski Bernd , Aeschlimann Salome , Schneider André 
Published: October 2024

AbstractThe parasitic protozoanTrypanosoma bruceihas a single unit mitochondrial genome linked to the basal body of the flagellum via the tripartite attachment complex (TAC). The TAC is crucial for mitochondrial genome segregation during cytokinesis. At the core of the TAC, the outer membrane protein TAC60 binds to the inner membrane protein p166, forming a permanent contact site between the two membranes. Although contact sites between mitochondrial membranes are common and serve various functions, their molecular architecture remains largely unknown. This study elucidates the interaction interface of the TAC60-p166 contact site. Usingin silico,in vitro, and mutationalin vivoanalyses, we identified minimal binding segments between TAC60 and p166. The p166 binding site in TAC60 consists of a short kinked α-helix that interacts with the C-terminal α- helix of p166. Despite the presence of conserved charged residues in either protein, electrostatic interactions are not necessary for contact site formation. Instead, the TAC60-p166 interaction is driven by the hydrophobic effect, as converting conserved hydrophobic residues in either protein to hydrophilic amino acids disrupts the contact site.Author summaryMitochondria are surrounded by two membranes and essential for nearly all eukaryotes. Contact sites between the two membranes are important for mitochondrial function. However, most contact sites are dynamic making their molecular architecture challenging to study. The tripartite attachment complex (TAC) of parasitic protozoanTrypanosoma bruceiconnects its compact mitochondrial genome with the basal body of the flagellum. This couples the segregation of the replicated mitochondrial genome to the old and new basal body. The TAC contains permanent contact sites formed by outer membrane protein TAC60 and the intermembrane space-exposed C-terminus of p166 of the inner membrane. We have used it as a model for a prototypical contact site. AlphaFold predictions and in vitro binding assays identified a small region in the intermembrane space region of TAC60 that binds p166 forming contact sites. In vivo expression of various TAC60 and/or p166 mutants followed by immunoprecipitations demonstrates that contact site formation is driven by the hydrophobic effect and independent of the conserved charged amino acids present at the TAC60-p166 interface. The TAC is unique to Kinetoplastids, understanding the molecular architecture of the TAC60-p166 contact site could therefore inform the development of drugs that disrupt this critical interaction.
Microgravity and low muon radiation affect viral pathogenesis and physiology inCaenorhabditis elegans
Authors: Villena-Giménez Ana , Castiglioni Victoria G. , Legarda Esmeralda G. , Muñoz-Sánchez Juan C. , González Rubén , Elena Santiago F. 
Published: October 2024

ABSTRACTSpaceflight exposes organisms to unprecedented environmental stresses, including microgravity and reduced muon radiation. These conditions are known to impact immune functions, potentially influencing the severity of viral infections. This study investigates the effects of microgravity and below-background radiation (i.e., reduced muon radiation flux) on Orsay virus infections inCaenorhabditis elegans. We assessedC. elegansfitness-related and developmental traits under a fully factorial combination of standard or microgravity with standard or below-background radiation conditions. Our findings reveal that microgravity and below-background radiation affect fecundity, with significant negative impacts on reproductive success and developmental abnormalities in infected animals. Additionally, the interaction between these environmental factors and viral infection led to complex effects on viral accumulation, which were increased under below-background radiation but reduced in microgravity. These results provide new insights into the interplay between abiotic stresses and viral infections in space, emphasizing the need for further research on the long-term impacts of spaceflight on immune function and pathogen-host interactions.
Epitranscriptomic rRNA fingerprinting reveals tissue-of-origin and tumor-specific signatures
Authors: Milenkovic Ivan , Cruciani Sonia , Llovera Laia , Lucas Morghan C , Medina Rebeca , Pauli Cornelius , Heid Daniel , Muley Thomas , Schneider Marc A. , Klotz Laura V. , Allgäuer Michael , Lattuca Ruben , LaFontaine Denis LJ , Müller-Tidow Carsten , Novoa Eva Maria 
Published: October 2024

ABSTRACTMammalian ribosomal RNA (rRNA) molecules are highly abundant RNAs, decorated with over 220 rRNA modifications. Previous works have shown that some rRNA modification types can be dynamically regulated; however, how and when the mammalian rRNA modification landscape is remodeled remains largely unexplored. Here, we employ direct RNA nanopore sequencing to chart the human and mouse rRNA epitranscriptome across tissues, developmental stages, cell types and disease. Our analyses reveal multiple rRNA sites that are differentially modified in a tissue- and/or developmental stage-specific manner, including previously unannotated modified sites. We demonstrate that rRNA modification patterns can be used for tissue and cell type identification, which we hereby term ‘epitranscriptomic fingerprinting’. We then explore rRNA modification patterns in normal-tumor matched samples from lung cancer patients, finding that epitranscriptomic fingerprinting accurately classifies clinical samples into normal and tumor groups from only 250 reads per sample, demonstrating the potential of rRNA modifications as diagnostic biomarkers.
Interpersonal Synchronization in Mother-Child Dyads: Neural and Motor Coupling as a Mechanism for Motor Learning and Development in Preschoolers
Authors: Nagy Péter , Béres Luca , Tóth Brigitta , Winkler István , Barthel Betty , Háden Gábor P. 
Published: October 2024

AbstractInterpersonal movement synchrony (IMS) and brain-to-brain coupling play a crucial role in social behavior across species. In humans, IMS is often studied in structured tasks that require specific body movements, while spontaneous, unstructured movements have received less attention. In this study, we investigated both structured and spontaneous motor coordination in mother-child dyads. We recorded upper-body kinematics and dual-EEG from mothers and their preschool children during motor tasks and spontaneous face-to-face interactions. Our findings show that mother-child dyads synchronize their movements and neural activity, particularly in gamma band oscillations. This motor and neural synchrony evolves across task repetitions, with a strong correlation between motor and neural measures. Further, we observed that only motor synchronization was significantly related to the child’s motor development stage, as assessed by the Movement Assessment Battery for Children. These results suggest that gamma band brain-to-brain coupling reflects joint motor coordination and mutual adaptation shaped by structured tasks and spontaneous interpersonal interactions.
Decision Confidence and Outcome Variability Optimally Regulate Separate Aspects of Hyperparameter Setting
Authors: Desender Kobe , Verguts Tom 
Published: October 2024

AbstractReinforcement learning models describe how agents learn about the world (value learning), and how they interact with their environment based on the learned information (decision policy). As in any optimization problem, it is important to set the process hyperparameters, a process which also is thought to be learned (meta-learning). Here, we test a key prediction of meta-learning frameworks, namely that there exist one or more meta-signals that govern hyperparameter setting. Specifically, we test whether decision confidence, in a context of varying outcome variability, informs hyperparameter setting. Participants performed a 2-armed bandit task with confidence ratings. Model comparison shows that confidence and outcome variability are differentially involved in hyperparameter setting. A high level of confidence in the previous choice decreased hyperparameter setting of decision noise on the current trial: when a trial was made with low confidence, the choice on the next trial tended to be more explorative (i.e. high decision noise). Outcome variability influenced another hyperparameter, the learning rate for positive prediction errors (thus affecting value learning). Both strategies are rational approaches that maximize earnings at different temporal loci: the modulation by confidence causes more frequent exploration early after a change point, the modulation by outcome variability is advantageous late after a change point. Finally, we show that (reported) confidence in value-based choices reflects the action value of the chosen option (irrespective of the unchosen value). In sum, decision confidence and outcome variability reflect distinct signals that optimally guide the setting of hyperparameters in decision policy and value learning, respectively.
Microbiome stability is linked to coral thermotolerance
Authors: Baquiran Jake Ivan P. , Quijano John Bennedick , van Oppen Madeleine J.H. , Cabaitan Patrick C. , Harrison Peter L. , Conaco Cecilia 
Published: October 2024

ABSTRACTCorals associate with a diverse community of prokaryotic symbionts that provide nutrition, antioxidants, and other protective compounds to their host. However, the influence of microbes on coral thermotolerance remains understudied. Here, we examined the prokaryotic microbial communities associated with colonies ofAcroporacf.tenuisthat exhibit high or low thermotolerance upon exposure to 33°C (heated) relative to 29°C (control). Using 16S rRNA sequencing, we show that the microbial community structure of allA.cf.tenuiscolonies were similar at control temperature. Thermotolerant colonies, however, had relatively greater abundance ofEndozoicomonas, Arcobacter,BifidobacteriumandLactobacillus. At elevated temperature, only thermosensitive colonies showed a distinct shift in their microbiome, with an increase in Flavobacteriales, Rhodobacteraceae, andVibrio,accompanying a marked bleaching response. Functional prediction indicated that prokaryotic communities associated with thermotolerant corals were enriched for genes related to metabolism, while microbiomes of thermosensitive colonies were enriched for cell motility and antibiotic compound synthesis. These differences may contribute to the variable performance of thermotolerant and thermosensitive corals under thermal stress. Identification of microbial taxa correlated with thermotolerance provides insights into beneficial bacterial groups that could be used for microbiome engineering to support reef health in a changing climate.
Reliable sensory processing of superficial cortical interneurons is modulated by behavioral state
Authors: Sweeney Carolyn G. , Thomas Maryse E. , Vattino Lucas G. , Smith Kasey E. , Takesian Anne E. 
Published: October 2024

SummaryThe GABAergic interneurons within cortical layer 1 (L1) integrate sensory and top-down inputs to modulate network activity and induce the plasticity underlying learning. However, little is known about how sensory inputs drive L1 interneuron activity. We used two-photon calcium imaging to measure the sound-evoked responses of two L1 interneuron populations expressing VIP (vasoactive intestinal peptide) or NDNF (neuron-derived neurotrophic factor) in mouse auditory cortex. We find that L1 interneurons respond to both simple and complex sounds with high trial-to-trial variability. However, these interneurons respond reliably to just a narrow range of stimuli, reflecting selectivity to spectrotemporal sound features. This response reliability is modulated by behavioral state and predicted by the activity of neighboring interneurons. Our data reveal that L1 interneurons exhibit sensory tuning and identify the modulation of response reliability as a potential mechanism by which L1 relays state-dependent cues to shape sensory representations.
Sequencing RNA from old, dried specimens reveals past viromes and properties of long-surviving RNA
Authors: Keene Alexandra H. , Stenglein Mark D. 
Published: October 2024

ABSTRACTRecovery of virus sequences from old samples provides an opportunity to study virus evolution and reconstruct historic virus-host interactions. Studies of old virus sequences have mainly relied on DNA or on RNA from fixed or frozen samples. The millions of specimens in natural history museums represent a potential treasure trove of old virus sequences, but it is not clear how well RNA survives in old samples. We experimentally assessed the stability of RNA in insects stored dry at room temperature over 72 weeks. Although RNA molecules grew fragmented, RNA yields remained surprisingly constant. RT-qPCR of host and virus RNA showed minimal differences between dried and frozen specimens. To assess RNA survival in much older samples we acquiredDrosophilaspecimens from North American entomological collections. We recovered sequences from known and novel viruses including several coding complete virus genomes from a fly collected in 1908. We found that the virome ofD. melanogasterhas changed little over the past century. Galbut virus, the most prevalent virus infection in contemporaryD. melanogaster, was also the most common in historic samples. Finally, we investigated the genomic and physical features of surviving RNA. RNA that survived was fragmented, chemically damaged, and preferentially double stranded or contained in ribonucleoprotein complexes. This showed that RNA - especially certain types of RNA – can survive in biological specimens over extended periods in the absence of fixation or freezing and confirms the utility of dried specimens to provide a clearer understanding of virus evolution.
Single-Sequence, Structure Free Allosteric Residue Prediction with Protein Language Models
Authors: Kannan Gokul R. , Hie Brian L. , Kim Peter S. 
Published: October 2024

AbstractLarge language models trained on protein amino acid sequences have shown the ability to learn general coevolutionary relationships at scale, which in turn contain useful structural and functional information. Here we show that attention maps, matrices of learned pairwise relationships between residues, also include information about allostery. This enables prediction of allosteric relationships with no task-specific training, requiring only a single input sequence and no structural information. Attention maps outperform state-of-the-art structure-based and sequence coevolution-based allosteric residue prediction models on a well-curated benchmark set of 24 allosteric proteins. For K-Ras, an allosterically regulated GTPase, attention maps correlate best with allosteric residues influencing binding identified in deep mutational scanning data. For the beta-2 adrenergic receptor, an allosterically regulated GPCR, attention maps correlate best when compared to experimental alanine-scanning mutational data identifying allosteric relationships influencing signaling. These results enable allosteric relationship prediction in a single-sequence, structure-free manner.
Aquifer microbial communities are highly variable in response to thermal arsenic mobilization
Authors: Chen Molly , Grégoire Daniel S. , St-Germain Pascale , Berdugo-Clavijo Carolina , Hug Laura A. 
Published: October 2024

ABSTRACTThermal recovery technologies forin-situbitumen extraction can result in the heating of surrounding aquifers, potentially mobilizing arsenic naturally present in the sediments to the groundwater. The relative toxicity of dissolved arsenic is related to its speciation, with As(V) being less toxic than As(III). Microorganisms have various mechanisms of arsenic resistance, including efflux and methylation. Microorganisms may also perform reduction/oxidation of As(V)/As(III) as part of their detoxification and/or metabolic pathways. We characterized the microbial communities along two aquifer transects associated with thermally mobilized arsenic near Northeastern Alberta oil sands deposits. 16S rRNA amplicons and metagenomic sequencing data of biomass from filtered groundwater indicated major changes in the dominant taxa between wells, especially those currently experiencing elevated arsenic concentrations. Annotation of arsenic-related genes indicated that efflux pumps (arsB, acr3), intracellular reduction (arsC) and methylation (arsM) genes were widespread amongst community members but comparatively few organisms encoded genes for arsenic respiratory reductases (arrA) and oxidases (arxA, aioA). While this indicates that microbes have the capacity to exacerbate arsenic toxicity by increasing the relative concentration of As(III), some populations of iron oxidizing and sulfate reducing bacteria (including novelGallionellaand Thermodesulfovibrionia populations) show potential for indirect bioremediation through formation of insoluble iron/sulfide minerals which adsorb or coprecipitate arsenic. An unusually high proportional abundance of a single Paceibacteria population that lacked arsenic resistance genes was identified in one high-arsenic well, and we discuss hypotheses for its ability to persist. Overall, this study describes how aquifer microbial communities respond to thermal and arsenic plumes, and predicts potential contributions of microbes to arsenic biogeochemical cycling under this disturbance.