bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pleiotropic effects of BAFF on the senescence-associated secretome and growth arrest
Authors: Rossi Martina , Anerillas Carlos , Idda Maria Laura , Munk Rachel , Shin Chang Hoon , Donegà Stefano , Tsitsipatis Dimitrios , Herman Allison B. , Martindale Jennifer L. , Yang Xiaoling , Piao Yulan , Mazan-Mamczarz Krystyna , Fan Jinshui , Ferrucci Luigi , De Supriyo , Abdelmohsen Kotb , Gorospe Myriam 
Published: October 2022

AbstractSenescent cells release a variety of cytokines, proteases, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Sustained SASP contributes to a pattern of chronic inflammation associated with aging and implicated in many age-related diseases. Here, we investigated the expression and function of the immunomodulatory cytokine BAFF (B-cell activating factor), a SASP protein, in multiple senescence models. We first characterized BAFF production across different senescence models, including senescent human diploid fibroblasts (WI-38, IMR-90) and monocytic leukemia cells (THP-1), and tissues of mice induced to undergo senescence. We then identified IRF1 (interferon response factor 1) as a transcription factor required for promotingBAFFmRNA transcription in senescence. We discovered that suppressing BAFF production decreased the senescent phenotype of both fibroblasts and monocyte-derived THP-1 cells, overall reducing IL6 secretion, SA-β-Gal staining, and γ-H2AX accumulation. Importantly, however, the influence of BAFF on the senescence program was cell type-specific: in monocytes, BAFF promoted the early activation of NF-κB and general SASP secretion, while in fibroblasts, BAFF contributed to the production and function of TP53 (p53). We propose that BAFF is elevated across senescence models and is a potential target for senotherapy.
Optogenetic manipulation of second messengers in neurons and cardiomyocytes with microbial rhodopsins and adenylyl cyclase
Authors: Hagio Hanako , Hosaka Shiori , Koyama Wataru , Song Aysenur Deniz , Narantsatsral Janchiv , Matsuda Koji , Shimizu Takashi , Hososhima Shoko , Tsunoda Satoshi P , Kandori Hideaki , Hibi Masahiko 
Published: October 2022

AbstractEven though microbial photosensitive proteins have been used for optogenetics, their use should be optimized to precisely control second messengersin vivo. We exploitedGtCCR4andKnChR, cation channelrhodopsins from algae,BeGC1, a guanylyl cyclase rhodopsin from a fungus, and photoactivated adenylyl cyclases (PACs) from cyanobacteria (OαPAC) or bacteria (bPAC), to control cell functions in zebrafish. Optical activation ofGtCCR4 andKnChR in the hindbrain reticulospinal V2a neurons, which are involved in locomotion, immediately induced swimming behavior, whereas activation ofBeGC1 or PACs was achieved at a short latency.KnChR had the highest locomotioninducing activity of all the channelrhodopsins examined. Activation ofGtCCR4 andKnChR in cardiomyocytes induced cardiac arrest, whereas activation ofbPAC gradually induced bradycardia.KnChR activation led to an increase in intracellular Ca2+in the heart, suggesting that depolarization caused cardiac arrest. These data suggest that these optogenetic tools can be used to reveal the roles of second messengers in various cell types in vertebrates.Impact statementWe identified efficient and useful microbial channelrhodopsin, guanylyl cyclase rhodopsin, and photoactivated adenylyl cyclase that regulate neural activity and cardiac function in zebrafish.Major subject areasNeuroscience, Cell biologyResearch organismZebrafish (Danio rerio)
Optogenetic manipulation of Gq- and Gi/o-coupled receptor signaling in neurons and heart muscle cells
Authors: Hagio Hanako , Koyama Wataru , Hosaka Shiori , Song Aysenur Deniz , Narantsatsral Janchiv , Matsuda Koji , Sugihara Tomohiro , Shimizu Takashi , Koyanagi Mitsumasa , Terakita Akihisa , Hibi Masahiko 
Published: October 2022

AbstractG protein-coupled receptors (GPCRs) transmit extracellular signals into the cell depending on the type of G protein. To analyze the functions of GPCR signaling, we developed optogenetic tools using animal G protein-coupled bistable rhodopsins that can be controlled into active and inactive states by light irradiation. We expressed Gq- and Gi/o-coupled bistable rhodopsins in hindbrain reticulospinal V2a neurons, which are involved in locomotion, or in cardiomyocytes of zebrafish. Light stimulation of the reticulospinal V2a neurons expressing Gq-coupled spider Rh1 resulted in an increase in the level of cytoplasmic Ca2+and evoked swimming behavior. Light stimulation of cardiomyocytes expressing the Gi/o-coupled mosquito Opn3, pufferfish TMT opsin, or lamprey parapinopsin induced cardiac arrest, and the effect was suppressed by treatment with pertussis toxin or barium, suggesting that Gi/o-dependent regulation of inward-rectifier K+channels controls cardiac function. These data indicate that these rhodopsins are useful for optogenetic control of GPCR-mediated signaling in neurons and cardiomyocytesin vivo.Impact statementAnimal G protein-coupled bistable rhodopsins can regulate Gq and Gi-mediated signaling in a light-dependent manner in neurons and cardiomyocytes, making them useful for analyzing roles of GPCR signalingin vivo.
GoldRush: Ade novolong read genome assembler with linear time complexity
Authors: Wong Johnathan , Coombe Lauren , Nikolić Vladimir , Zhang Emily , Nip Ka Ming , Sidhu Puneet , Warren René L , Birol Inanç 
Published: October 2022

AbstractMotivationCurrent state-of-the-art long readde novogenome assemblers follow the Overlap Layout Consensus (OLC) paradigm, an O(n2) algorithm in its naïve implementation. While the most time- and memory-intensive step of OLC —the all-vs-all sequencing read alignment process— was improved and reimplemented in modern long read assemblers, these tools still often require excessive computational memory when assembling a typical 50X human genome dataset.ResultsHere we present GoldRush, ade novogenome assembly algorithm with linear time complexity in the number of input long sequencing reads. We tested GoldRush on Oxford Nanopore Technologies datasets with different base error profiles describing the genomes of three human cell lines (NA24385, HG01243 and HG02055),Oryza sativa(rice), andSolanum lycopersicum(tomato). GoldRush achieved NGA50 lengths of 18.3-22.2 Mbp for the three human datasets, with two of the three assemblies having the fewest extensive misassemblies, and NGA50 lengths of 0.3 and 2.6 Mbp for the 373 Mbp and 824 Mbp genomes of rice and tomato, respectively. Further, GoldRush assembled all genomes within a day, using at most 54.5 GB of RAM. These results demonstrate that our algorithm and new assembly paradigm can be used to assemble large genomesde novoefficiently in compute memory space, with resulting assembly contiguity comparable to that of state-of-the-art OLC genome assemblers.Availabilityhttps://github.com/bcgsc/goldrush
The rostral intralaminar nuclear complex of the thalamus supports striatally-mediated action reinforcement
Authors: Cover Kara K. , Lieberman Abby G. , Heckman Morgan M. , Mathur Brian N. 
Published: October 2022

AbstractThe dorsal striatum (DS) mediates the selection of actions for reward acquisition necessary for survival. Striatal pathology contributes to several neuropsychiatric conditions, including aberrant selection of actions for specific rewards in addiction. A major source of glutamate driving striatal activity is the rostral intralaminar nuclei of the thalamus (rILN). Yet, the information that is relayed to the striatum to support action selection is unknown. Here we discovered that rILN neurons projecting to the DS integrated information from several subcortical and cortical sources and that these rILN→DS neurons stably signaled at two time points in mice performing an action sequence task reinforced by sucrose reward: action initiation and reward acquisition.In vivoactivation of this pathway increased the number of successful trials whereas inhibition decreased the number of successful trials. These findings illuminate a role for the rostral intralaminar nuclear complex in reinforcing actions.
Predictive modeling of antibiotic eradication therapy success for new-onsetPseudomonas aeruginosapulmonary infections in children with cystic fibrosis
Authors: Graña-Miraglia Lucía , Morales-Lizcano Nadia , Wang Pauline W. , Hwang David M. , Yau Yvonne C. W. , Waters Valerie J. , Guttman David S. 
Published: October 2022

ABSTRACTChronicPseudomonas aeruginosa(Pa) lung infections are the leading cause of mortality among cystic fibrosis (CF) patients; therefore, the eradication of new-onset Pa lung infections is an important therapeutic goal that can have long-term health benefits. The use of early antibiotic eradication therapy (AET) has been shown to eradicate the majority of new-onset Pa infections, and it is hoped that identifying the underlying basis for AET failure will further improve treatment outcomes. Here we generated random forest machine learning models to predict AET outcomes based on pathogen genomic data. We used a nested cross validation design, population structure control, and recursive feature selection to improve model performance and showed that incorporating population structure control was crucial for improving model interpretation and generalizability. Our best model, controlling for population structure and using only 30 recursively selected features, had an area under the curve of 0.87 for a holdout test dataset. The top-ranked features were generally associated with motility, adhesion, and biofilm formation.AUTHOR SUMMARYCystic fibrosis (CF) patients are susceptible to lung infections by the opportunistic bacterial pathogenPseudomonas aeruginosa(Pa) leading to increased morbidity and earlier mortality. Consequently, doctors use antibiotic eradication therapy (AET) to clear these new-onset Pa infections, which is successful in 60%-90% of cases. The hope is that by identifying the factors that lead to AET failure, we will improve treatment outcomes and improve the lives of CF patients. In this study, we attempted to predict AET success or failure based on the genomic sequences of the infecting Pa strains. We used machine learning models to determine the role of Pa genetics and to identify genes associated with AET failure. We found that our best model could predict treatment outcome with an accuracy of 0.87, and that genes associated with chronic infection (e.g., bacterial motility, biofilm formation, antimicrobial resistance) were also associated with AET failure.
A Clade-D Auxin Response Factor is a Major Regulator of Auxin Signaling inPhyscomitrium patens
Authors: Bascom Carlisle , Prigge Michael , Szutu Whitnie , Bantle Alexis , Irmak Sophie , Tu Daniella , Estelle Mark 
Published: October 2022

AbstractAuxin Response Factors (ARFs) are a family of transcription factors that are responsible for regulating gene expression in response to changes in auxin level. The analysis of ARF sequence and activity indicates that there are two major groups-activators and repressors. One clade of ARFs, clade-D, is sister to clade-A activating ARFs, but are unique in that they lack a DNA binding domain. Clade-D ARFs are present in lycophytes and bryophytes but absent in pteridophytes and spermatophytes. The transcriptional activity of clade-D ARFs, as well as how they regulate gene expression, is not well understood. Here, we report that clade-D ARFs are transcriptional activators in the model bryophyteP. patensand have a major role in the development of this species. Δarfd1,d2protonemata exhibit a delay in filament branching, as well as a delay in a key cell differentiation event. Additionally, leafy gametophore development in Δarfd1,d2lines lag behind wild-type. We present evidence that ARFd1 interacts with activating, but not repressing, ARFs. An ARFd1 hypomorph,arfd1T653L, cannot multimerize. Therefore, we propose a model by which clade-D ARFs enhance gene expression by oligomerizing to DNA-bound archetypal ARFs.
The N-terminal GTPase of Miro1 regulates oligomer formation
Authors: Eberhardt Emily L. , Mohamed Abdallah A. , Vos Seychelle , Cianfrocco Michael A. 
Published: October 2022

ABSTRACTThe outer-mitochondrial membrane protein Miro1 is critical for the regulation of mitochondrial trafficking. Miro1 contains two GTPase domains, where changes in the N-terminal GTPase nucleotide state strongly affects mitochondrial trafficking. Previous work showed that the GTP-locked mutation Miro1P13Vdecreases trafficking and affects mitochondrial dynamics. Despite showing a clear role in Miro1 function, the molecular basis for this activity remains unknown. Usingin vitroreconstitution, we demonstrate that Miro1 self-associates to form dimers and higher-ordered species. Structural characterization of Miro1P13Vsuggests that the oligomers adopt a range of conformationsin vitro. Additionally, Miro1P13Vhas diminished interaction with its downstream cargo adapter TRAK1. These results indicate that the NGTPase of Miro1 facilitates the formation of higher-ordered species and suggests that changes in the oligomeric state may regulate mitochondrial trafficking through reduced association with TRAK1.
Diet changes thermal acclimation capacity, but not acclimation rate in a marine ectotherm (Girella nigricans) during warming
Authors: Hardison Emily A. , Schwieterman Gail D. , Eliason Erika J. 
Published: October 2022

AbstractGlobal climate change is increasing thermal variability in coastal marine environments and the frequency, intensity, and duration of marine heatwaves. At the same time, nutritional resources are being altered by anthropogenic environmental changes. Marine ectotherms often cope with changes in temperature through physiological acclimation, which can take several weeks to occur and is a nutritionally demanding process. Here, we tested the hypothesis that different ecologically relevant diets (omnivorous, herbivorous, carnivorous) can impact thermal acclimation rate and capacity, using a temperate omnivorous fish as a model (opaleye;Girella nigricans). We measured acute thermal performance curves for maximum heart rate because cardiac function has been observed to set upper thermal limits in ectotherms. Opaleye acclimated rapidly after warming, but their thermal limits and acclimation rate were not affected by diet. However, the fish’s acclimation capacity for maximum heart rate was sensitive to diet, with fish in the herbivorous treatment displaying the smallest change in heart rate throughout acclimation. Mechanistically, ventricle fatty acid composition differed with diet treatment and was significantly related to cardiac performance in ways consistent with homoviscous adaptation. Our results suggest that diet is an important, but often overlooked, determinant of thermal performance in ectotherms on environmentally relevant timescales.
Role of horizontal gene transfers and microbial ecology in the evolution of fluxes through the tricarboxylic acid cycle
Authors: Sokolskyi Tymofii , DasSarma Shiladitya 
Published: October 2022

AbstractThe origin of carbon fixation is a fundamental question in astrobiology. While the Calvin cycle is the most active on the modern Earth, the reductive TCA cycle (rTCA) pathway for carbon fixation has been proposed to have played an important role in early evolution. In this study, we examined the evolution of key enzymes in the rTCA, which are rare in extant organisms, occurring in a few groups of Bacteria and Archaea. We investigated one of the least common reactions of this pathway, cleavage of citrate into oxaloacetate and acetyl-CoA, which can be performed by either a two-enzyme system (CCS/CCL) or a single enzyme (ACL) that is assumed to be the result of fusion of the two active sites into a single polypeptide. For broader context, we also studied functionally diverged homologs of these enzymes, succinyl-CoA synthetase (SCS) and citrate synthase (CS). Our phylogenetic analysis of these enzymes in Bacteria and Archaea shows that SCS, a homolog of CCS from distant bacterial taxa capable of citrate cleavage, are monophyletic, suggesting linked horizontal gene transfers of SCS and citrate cleavage enzymes. We also found evidence of the horizontal transfer of SCS from a clade of anaerobic Archaea (Archaeoglobi, Methanomicrobia or Crenarchaeota) to an ancestor of Cyanobacteria/Melainabacteria clade – both of whom share a succinate semialdehyde shunt in their oxidative TCA cycles. We also identified new bacterial and archaeal taxa for which complete rTCA cycles are theoretically possible, includingSyntrophobacter, Desulfofundulus, Beggiatoa, Caldithrix, Ca. Acidulodesulfobacterales andCa. Micrarachaeota. Finally, we suggest a possibility for syntrophically-regulated fluxes through oxidative and reductive TCA reactions in microbial communities particularly Haloarchaea-Nanohaloarchaea symbiosis and its implications for the Purple Earth hypothesis. We discuss how the inclusion of an ecological perspective in the studies of evolution of ancient metabolic pathways may be beneficial to understand origins of life.
Structure-based stabilization of SOSIP Env enhances recombinant ectodomain durability and yield
Authors: Wrapp Daniel , Mu Zekun , Thakur Bhishem , Janowska Katarzyna , Ajayi Oluwatobi , Barr Maggie , Parks Robert , Hahn Beatrice H. , Acharya Priyamvada , Saunders Kevin O. , Haynes Barton F. 
Published: October 2022

ABSTRACTThe envelope glycoprotein (Env) is the main focus of HIV-1 vaccine development due to its critical role in viral entry. Despite advances in protein engineering, many Env proteins remain recalcitrant to recombinant expression due to their inherent metastability, making biochemical and immunological experiments impractical or impossible. Here we report a novel proline-stabilization strategy to facilitate the production of prefusion Env trimers. This approach, termed “2P”, works synergistically with previously described SOSIP mutations and dramatically increases the yield of recombinantly expressed Env ectodomains without altering the antigenic or conformational properties of native Env. We determined that the 2P mutations function by enhancing the durability of the prefusion conformation and that this stabilization strategy is broadly applicable to evolutionarily and antigenically diverse Envs. These findings provide a new Env stabilization platform to facilitate biochemical research and expand the number of Env variants that can be developed as future HIV-1 vaccine candidates.
Multifocal two-photon excitation fluorescence microscopy reveals hop diffusion of H-Ras membrane anchors in epidermal cells of zebrafish embryos
Authors: Gora Radoslaw J. , Vlieg Redmar C. , Jonkers Sven , van Noort John , Schaaf Marcel J.M. 
Published: October 2022

ABSTRACTDevelopments in fluorescence microscopy techniques have enabled imaging of individual fluorescently labelled proteins in biological systems, and in the current study, a single-molecule microscopy (SMM) technique has been appliedin vivo, using the zebrafish embryo model. We have used multifocal two-photon excitation fluorescence microscopy (2PEFM) to study the dynamics of a GFP-fused H-Ras membrane-anchoring domain, GFP-C10H-Ras, in the epidermal cells of living embryos. In previous studies, a fast and a slow diffusing population of GFP-C10H-Ras molecules had been found. The application of the multifocal 2PEFM technique enabled us to focus on the slow diffusing population, which appears to occur in clusters that diffuse within microdomains of the epidermal cell membranes. Based on their mobility on a short timescale (≤ 1s) we could distinguish between a subpopulation that was diffusing and one that was virtually immobile. Owing to the multifocal 2PEFM imaging mode, we were able to dramatically reduce photobleaching which enabled us to follow the GFP-C10H-Ras particles over a prolonged time (> 3 s) and reconstruct their molecular trajectories of the diffusing subpopulation. These trajectories exhibited that the C10H-Ras particles continuously switch between a diffusing state and brief bursts of increased diffusion. As a result, they display an anomalous mobility pattern that can be referred to as hop diffusion. Taken together, this study demonstrates that multifocal 2PEFM offers a powerful approach to studying individual particles for prolonged periods of time, and that using this approach we were able to uncover the hopping behavior of GFP-C10H-Ras.SUMMARY STATEMENTBy application of the two-photon excitation single-molecule microscopy to living zebrafish embryos, anomalous diffusion modes of individual H-Ras membrane anchors in epidermal cells were found.
The Penultimate Step of Proteasomal ATPase Assembly is Mediated by a Nas2-Dependent Switch
Authors: Sekaran Suganya , Park Soyeon 
Published: October 2022

ABSTRACTThe proteasome holoenzyme is a complex molecular machine that degrades most proteins. In the proteasome holoenzyme, six distinct ATPase subunits (Rpt1 through Rpt6) enable protein degradation by injecting protein substrates into it. Individual Rpt subunits assemble into a heterohexameric “Rpt ring” in a stepwise manner, by binding to their cognate chaperones. Completion of the heterohexameric Rpt ring correlates with release of a specific chaperone, Nas2, however it is unclear whether and how this event may ensure proper Rpt ring assembly. Here, we examined the action of Nas2 by capturing the poorly characterized, penultimate step of heterohexameric Rpt ring assembly. We show that Nas2 uses steric hindrance to block premature progression of the penultimate step into the final step of Rpt ring assembly. Importantly, Nas2 can activate an assembly checkpoint via its steric activity, when the last ATPase subunit, Rpt1, cannot be added in a timely manner. This checkpoint can be relieved via Nas2 release, when it recognizes proper addition of Rpt1 to one side of its cognate Rpt5, and ATP hydrolysis by Rpt4 on the other side of Rpt5, allowing completion of Rpt ring assembly. Our findings reveal dual criteria for Nas2 release, as a mechanism to ensure both the composition and functional competence of a newly assembled proteasomal ATPase, to generate the proteasome holoenzyme.
Decision and response monitoring during working memory are sequentially represented in the human insula
Authors: Llorens A. , Bellier L. , Blenkmann A.O. , Ivanovic J. , Larsson P.G. , Lin J.J. , Endestad T. , Solbakk A.-K. , Knight R.T. 
Published: October 2022

AbstractEmerging research supports a role of the insula in human cognition. Here, we used intracranial EEG to investigate the spatiotemporal dynamics in the insula during a verbal working memory (vWM) task. We found robust effects for theta, beta, and high frequency activity (HFA) during probe presentation requiring a decision. Theta and beta band activity showed differential involvement across left and right insulae while sequential HFA modulations were observed along the anteroposterior axis. HFA in anterior insula tracked decision making and subsequent HFA was observed in posterior insula after the behavioral response. Our results provide electrophysiological evidence of engagement of different insula subregions in both decision-making and response monitoring during vWM and expand our knowledge of the role of the insula in complex human behavior.