bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell Maps for Artificial Intelligence: AI-Ready Maps of Human Cell Architecture from Disease-Relevant Cell Lines
Authors: Clark Timothy , Mohan Jillian , Schaffer Leah , Obernier Kirsten , Al Manir Sadnan , Churas Christopher P , Dailamy Amir , Doctor Yesh , Forget Antoine , Hansen Jan Niklas , Hu Mengzhou , Lenkiewicz Joanna , Levinson Maxwell Adam , Marquez Charlotte , Nourreddine Sami , Niestroy Justin , Pratt Dexter , Qian Gege , Thaker Swathi , Bélisle-Pipon Jean-Christophe , Brandt Cynthia , Chen Jake , Ding Ying , Fodeh Samah , Krogan Nevan , Lundberg Emma , Mali Prashant , Payne-Foster Pamela , Ratcliffe Sarah , Ravitsky Vardit , Sali Andrej , Schulz Wade , Ideker Trey 
Published: May 2024

AbstractThis article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools, status, and future directions. CM4AI is theFunctional Genomics Data Generation Projectin the U.S. National Institute of Health’s (NIH)Bridge2AIprogram. Its overarching mission is to produce ethical, AI-ready datasets of cell architecture, inferred from multimodal data collected for human cell lines, to enable transformative biomedical AI research.
SMC-mediated dosage compensation inC. elegansevolved in the presence of an ancestral nematode mechanism
Authors: Aharonoff Avrami , Kim Jun , Washington Aaliyah , Ercan Sevinç 
Published: May 2024

ABSTRACTMechanisms of X chromosome dosage compensation have been studied extensively in a few model species representing clades of shared sex chromosome ancestry. However, the diversity within each clade as a function of sex chromosome evolution is largely unknown. Here, we anchor ourselves to the nematodeCaenorhabditis elegans, for which a well-studied mechanism of dosage compensation occurs through a specialized structural maintenance of chromosomes (SMC) complex, and explore the diversity of dosage compensation in the surrounding phylogeny of nematodes. Through phylogenetic analysis of theC. elegans dosage compensation complex and a survey of its epigenetic signatures, including X-specific topologically associating domains (TADs) and X-enrichment of H4K20me1, we found that the condensin-mediated mechanism evolved recently in the lineage leading toCaenorhabditisthrough an SMC-4 duplication. Intriguingly, an independent duplication of SMC-4 and the presence of X-specific TADs inPristionchus pacificussuggest that condensin-mediated dosage compensation arose more than once. mRNA-seq analyses of gene expression in several nematode species indicate that dosage compensation itself is ancestral, as expected from the ancient XO sex determination system. Indicative of the ancestral mechanism, H4K20me1 is enriched on the X chromosomes inOscheius tipulae, which does not contain X-specific TADs or SMC-4 paralogs. Together, our results indicate that the dosage compensation system inC. elegansis surprisingly new, and condensin may have been co-opted repeatedly in nematodes, suggesting that the process of evolving a chromosome-wide gene regulatory mechanism for dosage compensation is constrained.Significance statementX chromosome dosage compensation mechanisms evolved in response to Y chromosome degeneration during sex chromosome evolution. However, establishment of dosage compensation is not an endpoint. As sex chromosomes change, dosage compensation strategies may have also changed. In this study, we performed phylogenetic and epigenomic analyses surroundingCaenorhabditis elegansand found that the condensin-mediated dosage compensation mechanism inC. elegansis surprisingly new, and has evolved in the presence of an ancestral mechanism. Intriguingly, condensin-based dosage compensation may have evolved more than once in the nematode lineage, the other time inPristionchus. Together, our work highlights a previously unappreciated diversity of dosage compensation mechanisms within a clade, and suggests constraints in evolving new mechanisms in the presence of an existing one.
Discovery of novel RNA viruses in commercially relevant seaweedsAlaria esculentaandSaccharina latissima
Authors: Dekker Rob J. , de Leeuw Wim C. , van Olst Marina , Ensink Wim A. , van Leeuwen Selina , Cohen Job , Timmermans Klaas R. , Breit Timo M. , Jonker Martijs J. 
Published: May 2024

AbstractSeaweeds are increasingly recognized as sustainable food sources; however, their large-scale cultivation faces challenges similar to land crops, including susceptibility to pathogens. Plant viruses pose a significant threat to global food security, yet little is known about the diversity of viruses in seaweeds. This study investigates virus-associated small interfering RNA (siRNA) responses in commercially relevant seaweed species to understand RNA virus diversity, particularly in edible varieties. Through small RNA sequencing of 16 samples fromSaccharina latissimaandAlaria esculenta, we identified three new RNA viruses Aev-NL1, Slv-NL2 and Slv-NL3, and one new DNA virus (phaeovirus). The partial genome of the new DNA virus was discovered in theA. esculentasamples and shared 67% DNA sequence identity with the major coat protein of the large double-stranded DNA phaeovirusFeldmannia irregularisvirus a. In four out of fiveA. esculentasamples, a new bisegmented ormycovirus-like RNA virus (Aev-NL1) was identified. A similar new virus, Slv-NL1, was found in previously publishedS. latissimaRNA-seq data, sharing 87% sequence identity with Aev-NL1. Lastly, two novel RNA viruses, Slv-NL2 and Slv-NL3, were discovered in all eightS. latissimasamples sharing limited similarity at the genome level but high sequence identity at protein level of both ORFs (>94%). Further investigation of the novel viruses’ presence across our limited set of samples revealed no conclusive associations with diseased seaweed phenotypes. The discovery of four new viruses in only a limited set of samples highlights the presence of previously unrecognized viral diversity in seaweed, thereby underscoring the importance of understanding viral diversity in seaweed as its virome is currently understudied.
Regulation of dopamine release by tonic activity patterns in the striatal brain slice
Authors: Boumhaouad Siham , Makowicz Emily A , Choi Sejoon , Bouhaddou Nezha , Balla Jihane , Taghzouti Khalid , Sulzer David , Mosharov Eugene V. 
Published: May 2024

ABSTRACTVoluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons that extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: a low-frequency tonic activity that is intrinsically generated and superimposed high-frequency phasic bursts that are driven by synaptic inputs.Ex vivoacute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics thanin vivorecordings. To investigate the relationship between phasic and tonic neuronal activity, we stimulated the slice in patterns intended to mimic tonic activity, which were interrupted by a series of burst stimuli. Conditioning the striatal slice with low-frequency activity altered DA release triggered by high-frequency bursts and produced kinetic parameters that resemble thosein vivo. In the absence of applied tonic activity, nicotinic acetylcholine receptor and D2 dopamine receptor antagonists had no significant effect on neurotransmitter release driven by repeated burst activity in the striatal brain slice. In contrast, in tonically stimulated slices, D2 receptor blockade decreased the amount of DA released during a single burst and facilitated DA release in subsequent bursts. This experimental system provides a means to reconcile the difference in the kinetics of DA releaseex vivoandin vivoand provides a novel approach to more accurately emulate pre- and post-synaptic mechanisms that control axonal DA releasein vivo.Abstract Figure
Anin vivo“turning model” reveals new RanBP9 interactions in lung macrophages
Authors: Kajimura Yasuko , Tessari Anna , Orlacchio Arturo , Thoms Alexandra , Cufaro Maria Concetta , Marco Federica Di , Amari Foued , Chen Min , Soliman Shimaa H.A. , Rizzotto Lara , Zhang Liwen , Amann Joseph , Carbone David P. , Ahmed Amer , Fiermonte Giuseppe , Freitas Mike , Lodi Alessia , Boccio Piero Del , Palmieri Dario , Coppola Vincenzo 
Published: May 2024

AbstractThe biological functions of the scaffold protein Ran Binding Protein 9 (RanBP9) remain elusive in macrophages or any other cell type where this protein is expressed together with its CTLH (C-terminal to LisH) complex partners. We have engineered a new mouse model, named RanBP9-TurnX, where RanBP9 fused to three copies of the HA tag (RanBP9-3xHA) can be turned into RanBP9-V5 tagged upon Cre-mediated recombination. We created this model to enable stringent biochemical studies at cell type specific level throughout the entire organism. Here, we have used this tool crossed with LysM-Cre transgenic mice to identify RanBP9 interactions in lung macrophages. We show that RanBP9-V5 and RanBP9-3xHA can be both co-immunoprecipitated with the known members of the CTLH complex from the same whole lung lysates. However, more than ninety percent of the proteins pulled down by RanBP9-V5 differ from those pulled-down by RanBP9-HA. The lung RanBP9-V5 associated proteome includes previously unknown interactions with macrophage-specific proteins as well as with players of the innate immune response, DNA damage response, metabolism, and mitochondrial function. This work provides the first lung specific RanBP9-associated interactome in physiological conditions and reveals that RanBP9 and the CTLH complex could be key regulators of macrophage bioenergetics and immune functions.
Detection of Nontoxic BoNT/A Levels in Post-Facial Botox Injection Breastmilk using a Multi-technique Approach
Authors: Gu Helene , Xu Zhenyu , Koviazina Renata , Tan Pengcheng , Zheng Changcheng , Kappes Ferdinand , Kotsifaki Domna G. , Shen Fangrong , Tsigkou Anastasia 
Published: May 2024

AbstractBackgroundThe use of cosmetic Botox (Botulinum Neurotoxin Type A, BoNT/A ) has become increasingly prevalent. Particularly after pregnancy, postpartum depression represents one major factor motivating women to use Botox even during the lactation and breastfeeding period. Currently, there is limited understanding of the impact of Botox on lactation and the potential of its active component passing into breastmilk and affecting the infant.MethodsBreastmilk samples were acquired from five women aged between 28 - 45 through a clinic in Suzhou, Jiangsu, P.R. China. Three sample sets ranged from 1 hour to 1 year after facial Botox treatments (64 U), whereas the remaining two sample sets were from women who never received Botox treatment. BoNT/A concentrations in samples were detected using standard Enzyme-Linked Immunosorbent Assay (ELISA), unreduced and reduced Western Blotting, confocal micro-Raman Spectroscopy, and Mass Spectrometry(LC-MS).FindingsFrom ELISA, breastmilk BoNT/A concentrations peaked at 33.4 pg/mL 4 days after Botox injection. BoNT/A concentrations were highest overall in the first week and around two months after injection. While non-reducing polyacrylamide gel electrophoresis (PAGE) showed a protein band of 150 kDa peaking at 48 hours, reduced SDS-PAGE detected a 100 kDa protein first peaking at 72 hours, then re-emerging after 7 days, respectively, and in line with previous observations by others. Interestingly, micro-Raman spectroscopy indicated additional Raman peaks at 6 hours and 48 hours that were not present in other breastmilk samples which were evaluated in this study. However, no clear indication of BoNT/A was detected in Mass Spectrometry (LC-MS).InterpretationThe amount of BoNT/A in breastmilk peaks around 48 hours, and at 2 months after facial injection. Even over a year after injection, BoNT/A can be detected. However, all quantities of BoNT/A detected in this study are highly likely to be safe for infants. Additionally, our study suggests that alternative methods, besides ELISA, may be utilized for the rapid detection of low concentrations of BoNT/A in body fluid samples.FundingDuke Kunshan University Start-Up funds, Duke Kunshan University Undergraduate Studies Signature Work Research Grant, Synear and Wang-Cai Biochemistry grants, and Kunshan Municipal Government research funding.Graphical AbstractHighlightsBoNT/A was detected in the breastmilk of 3 women after facial Botox injections of 64 U.Toxin levels peaked in the first week and at around 2 months after injection.All detected levels (up to 33.40 pg/mL) were significantly below the lethal dose for newborns.
Laboratory tests for influenza and the respiratory syncytial virus may be used as a proxy for associated hospitalizations in Canada
Authors: Champredon David 
Published: May 2024

AbstractIn Canada, the national number of hospital admissions associated with influenza and respiratory syncytial virus (RSV) is usually available about three months after admission. This delay hampers real-time analysis involving hospitalization data, like, for example, epidemic forecasting. Here, using a mixed-effects model on 15 years of data covering about 70% of the Canadian population, we show that these hospitalizations can be approximated using the number of laboratory tests positive for influenza A and RSV, a data stream publicly reported much more rapidly, about two weeks after symptoms onset.
Clostridioides difficilebinary toxin CDT induces biofilm-like persisting microcolonies
Authors: Meza Torres Jazmin , Tinevez Jean-Yves , Crozouls Aline , Mary Héloïse , Kim Minhee , Hunault Lise , Chamorro-Rodriguez Susan , Lejal Emilie , Altamirano-Silva Pamela , Gobaa Samy , Peltier Johann , Chassaing Benoit , Dupuy Bruno 
Published: May 2024

SUMMARYClinical symptoms ofClostridioides difficileinfection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate production of CDT binary toxin by clinical strains ofClostridioides difficilewith higher relapse rates. Although the mechanism of action of CDT on host cells is known, its exact contribution to CDI is still unclear. To understand the physiological role of CDT during CDI, we established two hypoxic relevant intestinal models, Transwell and Microfluidic Intestine-on-Chip systems. Both were challenged with the epidemic strain UK1 CDT+and its isogenic CDT-mutant. We report that CDT binary toxin induces mucin-associated microcolonies that increaseC. difficilecolonization and display biofilm-like properties by enhancingC. difficileresistance to vancomycin but not to fidaxomicin, a biofilm disrupting antibiotic. Importantly, biofilm- like CDT-dependent microcolonies were also observed in the caecum and colon of infected mice. Hence, our study shows that CDT toxin induces biofilm-like microcolonies, increasingC. difficilecolonization and persistence.
SH3BP2 regulates the organization of the neuromuscular synapses through protein-driven phase separation
Authors: Pradhan Bhola Shankar , Bernadzki Krzysztof , Bandaruk Yauhen , Siudzińska Anna , De Cicco Teresa , Gawor Marta , Krzemień Joanna , Chodaczek Grzegorz , Hashemolhosseini Said , Prószyński Tomasz J. 
Published: May 2024

AbstractThe molecular mechanisms underlying the development and maintenance of the neuromuscular junction are poorly understood, even though the malfunction of these specialized synapses is associated with severe genetic and autoimmune disorders. The identity of factors controlling the maintenance mechanisms of postsynaptic acetylcholine receptors (AChR) in high-density has been elusive and is of great interest to the pharma industry, searching for possible new targets for disease interventions. Here, we report the identification of a scaffold protein SH3BP2, which exhibits polyvalent interaction with the dystrophin-glycoprotein complex (DGC) and AChR pentamers, promoting AChR clustering through phase separation. Muscle-specific SH3BP2 deletion in mice leads to impaired organization of the neuromuscular synapses, defects in synaptic transmission, and reduced muscle strength. Our studies identified a novel regulator of the postsynaptic machinery involved in clustering AChR and linking it to the DGC.
Multifaceted confidence in exploratory choice
Authors: Solopchuk Oleg , Dayan Peter 
Published: May 2024

AbstractOur choices are typically accompanied by a feeling of confidence - an internal estimate that they are correct. Correctness, however, depends on our goals. For example, exploration-exploitation problems entail a tension between short- and long-term goals: finding out about the value of one option could mean foregoing another option that is apparently more rewarding. Here, we hypothesised that after making an exploratory choice that involves sacrificing an immediate gain, subjects will be confident that they chose a better option for long-term rewards, but not confident that it was a better option for immediate reward. We asked 250 subjects across 2 experiments to perform a varying-horizon two-arm bandits task, in which we asked them to rate their confidence that their choice would lead to more immediate, or more total reward. Confirming previous studies, we found a significant increase in exploration with increasing trial horizon, but, contrary to our predictions, we found no difference between confidence in immediate or total reward. This dissociation is further evidence for a separation in the mechanisms involved in choices and confidence judgements.
Meta-Control Demands at the Beginning of Extended Tasks are Categorically Different from Control Demands During Their Subsequent Execution
Authors: Akgur Berhan F. , Gezici Tamer , Oymagil Elif , Farooqui Ausaf A. 
Published: May 2024

AbstractThe well-known activation of frontoparietal regions forms the basis of neuroscientific accounts of cognitive control. Control interventions that activate frontoparietal regions also generate a characteristic psychophysiological signature that, amongst others, is accompanied by increased pupil size. Here, we characterize a distinct but key aspect of cognitive control that deactivates these frontoparietal regions and decreases pupil size.Our goals are completed through extended tasks that are hierarchically controlled and executed as a single entity despite consisting of numerous steps (e.g., ‘preparing coffee’, ‘writing emails’). This is achieved through higher-level programs instantiated at the beginning of their execution that will go on to organize cognition and instantiate various control interventions during the ensuing task execution.Difficult episodes begin with the instantiation of more complex higher-level programs that will go on to organize a more complex set of control interventions. However, the demands related to instantiating these more complex programs are likely to be distinct from those related to control interventions. Control interventions, like selective attention, inhibition, etc., involve making goal-directed changes in sensory and motor regions to select the correct incoming information and action. In contrast, instantiating higher-level programs involves embodying the set of commands that will go on to make the relevant goal-directed neurocognitive changes later in the ensuing extended task by organizing and instantiating the correct set of control interventions.Across four experiments, we show that while executing difficult episodes activates frontoparietal regions and increases pupil size, the beginning of these difficult episodes, i.e., junctures where more complex higher-level programs are instantiated, deactivates these same frontoparietal regions and decreases pupil size. We thus show that cognitive control related to difficult extended tasks involves categorically different demands at the beginning compared to during their subsequent execution.
Altered striosome-matrix distribution and activity of striatal cholinergic interneurons in a model of autism-linked repetitive behaviors
Authors: Molitor Jordan , Graniou Juliette , Salin Pascal , Castets Francis , Fatmi Ahmed , Kerkerian-Le Goff Lydia , Fasano Laurent , Caubit Xavier , Gubellini Paolo 
Published: May 2024

ABSTRACTRepetitive behaviors are cardinal features of many brain disorders, including autism spectrum disorder (ASD). We previously associated dysfunction of striatal cholinergic interneurons (SCINs) with repetitive behaviors in a mouse model based on conditional deletion of the ASD-related geneTshz3in cholinergic neurons (Chat-cKO). Here, we provide evidence linking SCIN abnormalities to the unique organization of the striatum into striosome and matrix compartments, whose imbalances are implicated in several pathological conditions.Chat-cKOmice exhibit altered relationship between the embryonic birthdate of SCINs and their adult striosome-matrix distribution, leading to an increased proportion of striosomal SCINs. In addition, the ratio of striosomal SCINs with slow-irregularvs. sustained-regular firing is increased, which translates into decreased activity, further stressing the striosome-matrix imbalance. These findings provide novel insights onto the pathogenesis of ASD-related stereotyped behaviors by pointing to abnormal developmental compartmentalization and activity of SCINs as a substrate.
Navigating directed evolution efficiently: optimizing selection conditions and selection output analysis
Authors: Handal-Marquez Paola , Nguyen Hoai , Pinheiro Vitor B. 
Published: May 2024

AbstractDirected evolution is a powerful tool that can bypass gaps in our understanding of the sequence-function relationship of proteins and still isolate variants with desired activities, properties, and substrate specificities. The rise of directed evolution platforms for polymerase engineering has accelerated the isolation of xenobiotic nucleic acids (XNAs) synthetases and reverse transcriptases (RTs) capable of processing a wide array of unnatural XNAs which have numerous therapeutic and biotechnological applications. Still, the current generation of XNA polymerases functions with significantly lower efficiency than the natural counterparts and retains a significant level of DNA polymerase activity which limits theirin vivoapplications. Although directed evolution approaches are continuously being developed and implemented to improve XNA polymerase engineering, the field lacks an in-depth analysis of the effect of selection parameters, library construction biases and sampling biases. Focusing on the directed evolution pipeline for DNA and XNA polymerase engineering, this work sets out a method for understanding the impact of selection conditions on selection success and efficiency. We also explore the influence of selection conditions on fidelity at the population and individual mutant level. Additionally, we explore the sequencing coverage requirements in directed evolution experiments, which differ from genome assembly and other-omicsapproaches. This analysis allowed us to identify the sequencing coverage threshold for the accurate and precise identification of significantly enriched mutants. Overall, this study introduces a robust methodology for optimizing selection protocols, which effectively streamlines selection processes by employing small libraries and cost-effective NGS sequencing. It provides valuable insights into critical considerations, thereby enhancing the overall effectiveness and efficiency of directed evolution strategies applicable to enzymes other than the ones considered here.