bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Out of sight, out of mind”. The antagonistic role of the transcriptional memory associated with repeated acoustic stimuli on the priming of plant defense
Authors: Hadj-Amor Khaoula , Léger Ophélie , Raffaele Sylvain , Kovacic Magdalena , Duclos Aroune , Carvalho-Silva Pedro , Garcia Frédérick , Barbacci Adelin 
Published: May 2024

AbstractFacilitating plant defense through priming holds significant promise for advancing sustainable crop health practices. The primed state of plants is correlated with a more rapid and efficient response, achievable by subjecting plants to recurrent stressors. Consequently, priming constitutes a dynamic transitional process between two distinct biological states, necessitating the establishment and maintenance of transcriptional memory mechanisms. Research on transcriptional memory has revealed molecular mechanisms including protein and transcription factor accumulation, as well as epigenetic modulations. Nonetheless, there remains a dearth of understanding regarding the interplay among the dynamics of transcriptional stress memory, its preservation, and the resultant emergent properties conferred upon the organism once primed. Here, we found that the robustness of transcriptional memory associated with repeated mechanical stimuli played an antagonistic role in the priming of plant defense. Incorporating experiments and computational modeling, we have analyzed the transcriptional stress memory ofArabidopsis thalianasubjected to daily acoustic stimulations. The observed enhanced resistance to the pathogenSclerotinia sclerotiorumfollowing three rounds of repeated acoustic stimulations is attributed to three primary mechanisms: the activation of a first line of defense in non-inoculated plants, an increase defense-associated gene diversification, and gene priming. These mechanisms are sustained by a transcriptional stress memory involving thousands of genes, likely regulated mostly by transcription factor cascades. Upon comparing the predictions of the transcriptional stress memory model with experimental outcomes, we propose that priming does not arise from the sequential activation of different pathways but rather from the simultaneous modulation of a broad spectrum of pathways. Pathway redundancy in the transcriptional memory topology imparts robustness to plant defense priming. Consequently, primed plants exhibit independence from limited genetic variations, preventing critical loss of resistance observed in naive plants. Pathway redundancies also imply strong limitations in increasing plant defense. Thus, plants remain unaffected by an increase in the daily rate of RAS and exhibited a stress memorization time limited to 1.5 days.
A continuous dynamic genome-scale model explains batch fermentations led by species of theSaccharomycesgenus
Authors: Moimenta Artai R. , Troitiño-Jordedo Diego , Henriques David , Contreras-Ruíz Alba , Minebois Romain , Morard Miguel , Barrio Eladio , Querol Amparo , Balsa–Canto Eva 
Published: May 2024

ABSTRACTBatch fermentation is a biotechnological dynamic process that produces various products by employing microorganisms that undergo different growth phases: lag, exponential, growth-non-growth, stationary, and decay. Genome-scale constrained-based models are commonly used to explore the phenotypic potential of these microorganisms.Previous studies have primarily used dynamic Flux Balance Analysis (dFBA) to elucidate the metabolism during the exponential phase. However, this approach falls short in addressing the multi-phase nature of the process and secondary metabolism, posing significant challenges to our understanding of batch fermentation. A recent attempt at a solution was a discontinuous, multi-phase, multi-objective dFBA implementation.However, this approximation lacks the mechanistic connection between phases, limiting its applicability in predicting intracellular fluxes during batch fermentation.To overcome these limitations, we combined a novel continuous model with a genome-scale model to predict the distribution of intracellular fluxes throughout the batch fermentation process. The proposed model includes empirical descriptions of regulation that automatically identify the transition between phases. Its application to explain primary and secondary metabolism ofSaccharomycesspecies in batch fermentation results in biological insights that are in good agreement with the previous literature. The ability to account for all process phases and explain secondary metabolism makes this model a valuable and easy-to-use tool for exploring novel fermentation processes.IMPORTANCEThis research proposes a novel dynamic genome-scale modelling approach for batch fermentation, a crucial process widely used to produce a diverse range of products such as biofuels, enzymes, pharmaceuticals, and food products or ingredients.The proposed approach automatically accounts for the transitions between different phases of the fermentation process (lag, exponential, growth-no-growth, and stationary). This is a significant advancement over previous methods that required different model formulations for different phases.We have successfully applied this modelling approach to explore the primary and secondary metabolism of three yeast species under batch fermentation conditions. The model accurately explained experimental data and provided biological insights consistent with previous research findings, instilling confidence in its reliability and accuracy.The ability of this modelling approach to explain primary and secondary metabolism makes it a valuable tool for designing novel, more efficient, and effective fermentation processes, which could have far-reaching implications in industrial biotechnology.
Post-Transcriptional Modular Synthetic Receptors
Authors: Zhang Xiaowei , Mille-Fragoso Luis S. , Kaseniit K. Eerik , Lee Arden P. , Zhang Meng , Call Connor C. , Hu Yixin , Xie Yunxin , Gao Xiaojing J. 
Published: May 2024

AbstractInspired by the power of transcriptional synthetic receptors and hoping to complement them to expand the toolbox for cell engineering, we establish LIDAR (Ligand-Induced Dimerization Activating RNA editing), a modular post-transcriptional synthetic receptor platform that harnesses RNA editing by ADAR. LIDAR is compatible with various receptor architectures in different cellular contexts, and enables the sensing of diverse ligands and the production of functional outputs. Furthermore, LIDAR can sense orthogonal signals in the same cell and produce synthetic spatial patterns, potentially enabling the programming of complex multicellular behaviors. Finally, LIDAR is compatible with compact encoding and can be delivered as synthetic mRNA. Thus, LIDAR expands the family of synthetic receptors, holding the promise to empower basic research and therapeutic applications.
Transformation of an olfactory placode-derived cell into one with stem cell characteristics by disrupting epigenetic barriers
Authors: Abbas Ghazia , Vyas Rutesh , Noble Joyce C. , Lin Brian , Lane Robert P. 
Published: May 2024

ABSTRACTThe mammalian olfactory neuronal lineage is regenerative, and accordingly, maintains a population of pluripotent cells that replenish olfactory sensory neurons and other olfactory cell types during the life of the animal. Moreover, in response to acute injury, the early transit amplifying cells along the olfactory sensory neuronal lineage are able to de-differentiate to shift resources in support of tissue restoration. In order to further explore plasticity of various cellular stages along the olfactory sensory neuronal lineage, we challenged the epigenetic stability of two olfactory placode-derived cell lines that model immature olfactory sensory neuronal stages. We found that perturbation of theEhmt2chromatin modifier transformed the growth properties, morphology, and gene expression profiles towards states with several stem cell characteristics. This transformation was dependent on continued expression of the large T-antigen, and was enhanced by Sox2 over-expression. These findings may provide momentum for exploring inherent cellular plasticity within early cell types of the olfactory lineage, as well as potentially add to our knowledge of cellular reprogramming.SUMMARY STATEMENTDiscovering how epigenetic modifications influence olfactory neuronal lineage plasticity offers insights into regenerative potential and cellular reprogramming.
A metabolic atlas of mouse aging
Authors: Pilley Steven E , Awad Dominik , Latumalea Djakim , Esparza Edgar , Zhang Li , Shi Xuanyi , Unfried Maximilian , Wang Shuo , Mulondo Racheal , Kashyap Sriraksha Bharadwaj , Moaddeli Darius , Sajjakulnukit Peter , Sutton Damien , Wong Harrison , Coakley Aeowynn J. , Garcia Gilberto , Higuchi-Sanabria Ryo , Liu Sophia , Yu Bingfei , Tu William B , Kennedy Brian K. , Lyssiotis Costas A , Mullen Peter J 
Published: May 2024

AbstractHumans are living longer, but this is accompanied by an increased incidence of age-related chronic diseases. Many of these diseases are influenced by age-associated metabolic dysregulation, but how metabolism changes in multiple organs during aging in males and females is not known. Answering this could reveal new mechanisms of aging and age-targeted therapeutics. In this study, we describe how metabolism changes in 12 organs in male and female mice at 5 different ages. Organs show distinct patterns of metabolic aging that are affected by sex differently. Hydroxyproline shows the most consistent change across the dataset, decreasing with age in 11 out of 12 organs investigated. We also developed a metabolic aging clock that predicts biological age and identified alpha-ketoglutarate, previously shown to extend lifespan in mice, as a key predictor of age. Our results reveal fundamental insights into the aging process and identify new therapeutic targets to maintain organ health.
Neuronal and oligodendroglial but not astroglial tau translates to in vivo tau-PET signals in primary tauopathies
Authors: Slemann Luna , Gnörich Johannes , Hummel Selina , Bartos Laura M. , Klaus Carolin , Kling Agnes , Kusche-Palenga Julia , Kunte Sebastian T. , Kunze Lea H. , Englert Amelie L. , Li Yunlei , Vogler Letizia , Katzdobler Sabrina , Palleis Carla , Bernhardt Alexander , Jäck Alexander , Zwergal Andreas , Hopfner Franziska , Römer Sebastian , Biechele Gloria , Stöcklein Sophia , Bischof Gerard , van Eimeren Thilo , Drzezga Alexander , Sabri Osama , Barthel Henryk , Respondek Gesine , Grimmer Timo , Levin Johannes , Herms Jochen , Paeger Lars , Willroider Marie , Beyer Leonie , Höglinger Günter U. , Roeber Sigrun , Franzmeier Nicolai , Brendel Matthias 
Published: May 2024

SummaryTau-PET receives growing interest as an imaging biomarker for the 4-repeat tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau-PET signals is still unclear. Therefore, we conducted a longitudinal [18F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and found elevated [18F]PI-2620 PET signal in the presence of high neuronal tau. Cell sorting after radiotracer injection in vivo revealed higher tracer uptake in single neurons compared to astrocytes of PS19 mice. Regional [18F]PI-2620 tau-PET signals during lifetime correlated with abundance of fibrillary tau in subsequent autopsy samples of PSP patients and disease controls. In autoradiography, tau-positive neurons and oligodendrocytes with high AT8 density but not tau-positive astrocytes were the driver of [18F]PI-2620 autoradiography signals in PSP. In summary, neuronal and oligodendroglial tau constitutes the dominant source of tau-PET radiotracer binding in 4-repeat-tauopathies, yielding the capacity to translate to an in vivo signal.
Negative Selection Allows DNA Mismatch Repair-Deficient Mouse FibroblastsIn Vitroto Tolerate High Levels of Somatic Mutations
Authors: Zhang Lei , Lee Moonsook , Hao Xiaoxiao , Ehlert Joseph , Chi Zhongxuan , Jin Bo , Maslov Alexander Y. , Barabási Albert-László , Hoeijmakers Jan H. J. , Edelmann Winfried , Vijg Jan , Dong Xiao 
Published: May 2024

SummarySubstantial numbers of somatic mutations have been found to accumulate with age in different human tissues. Clonal cellular amplification of some of these mutations can cause cancer and other diseases. However, it is as yet unclear if and to what extent an increased burden of random mutations can affect cellular function without clonal amplification. We tested this in cell culture, which avoids the limitation that an increased mutation burdenin vivotypically leads to cancer. We performed single-cell whole-genome sequencing of primary fibroblasts from DNA mismatch repair (MMR) deficientMsh2-/-mice and littermate control animals after long-term passaging. Apart from analyzing somatic mutation burden we analyzed clonality, mutational signatures, and hotspots in the genome, characterizing the complete landscape of somatic mutagenesis in normal and MMR-deficient mouse primary fibroblasts during passaging. While growth rate ofMsh2-/-fibroblasts was not significantly different from the controls, the number ofde novosingle-nucleotide variants (SNVs) increased linearly up until at least 30,000 SNVs per cell, with the frequency of small insertions and deletions (INDELs) plateauing in theMsh2-/-fibroblasts to about 10,000 INDELS per cell. We provide evidence for negative selection and large-scale mutation-driven population changes, including significant clonal expansion of preexisting mutations and widespread cell-strain-specific hotspots. Overall, our results provide evidence that increased somatic mutation burden drives significant cell evolutionary changes in a dynamic cell culture system without significant effects on growth. Since similar selection processes against mutations preventing organ and tissue dysfunction during aging are difficult to envision, these results suggest that increased somatic mutation burden can play a causal role in aging and diseases other than cancer.
Functional brain network dynamics of brooding in depression: insights from real-time fMRI neurofeedback
Authors: Ganesan Saampras , Misaki Masaya , Zalesky Andrew , Tsuchiyagaito Aki 
Published: May 2024

AbstractBackgroundBrooding is a critical symptom and prognostic factor of major depressive disorder (MDD), which involves passively dwelling on self-referential dysphoria and related abstractions. The neurobiology of brooding remains under characterized. We aimed to elucidate neural dynamics underlying brooding, and explore their responses to neurofeedback intervention in MDD.MethodsWe investigated functional MRI (fMRI) dynamic functional network connectivity (dFNC) in 36 MDD subjects and 26 healthy controls (HCs) during rest and brooding. Rest was measured before and after fMRI neurofeedback (MDD-active/sham: n=18/18, HC-active/sham: n=13/13). Baseline brooding severity was recorded using Ruminative Response Scale - Brooding subscale (RRS-B).ResultsFour recurrent dFNC states were identified. Measures of time spent were not significantly different between MDD and HC for any of these states during brooding or rest. RRS-B scores in MDD showed significant negative correlation with measures of time spent in dFNC state 3 during brooding (r=-0.5, p= 1.7E-3, FDR-significant). This state comprises strong connections spanning several brain systems involved in sensory, attentional and cognitive processing. Time spent in this anti-brooding dFNC state significantly increased following neurofeedback only in the MDD active group (z=-2.09, p=0.037).LimitationsThe sample size was small and imbalanced between groups. Brooding condition was not examined post-neurofeedback.ConclusionWe identified a densely connected anti-brooding dFNC brain state in MDD. MDD subjects spent significantly longer time in this state after active neurofeedback intervention, highlighting neurofeedback’s potential for modulating dysfunctional brain dynamics to treat MDD.
Stronger bat predation and weaker environmental constraints predict longer moth tails
Authors: Rubin Juliette J. , Campbell Caitlin J. , Carvalho Ana Paula S. , St. Laurent Ryan A. , Crespo Gina I. , Pierson Taylor L. , Guralnick Robert P. , Kawahara Akito Y. 
Published: May 2024

AbstractElaborate traits evolve via intense selective pressure, overpowering ecological constraints. Hindwing tails that thwart bat attack have repeatedly originated in moon moths (Saturniidae), with longer tails having greater anti-predator effect. Here, we take a macroevolutionary approach to evaluate the evolutionary balance between predation pressure and possible limiting environmental factors on tail elongation. To trace the evolution of tail length across time and space, we inferred a time-calibrated phylogeny of the entirely tailed moth group (Actias + Argema) and performed ancestral state reconstruction and biogeographical analyses. We generated metrics of predation via estimates of bat abundance from nearly 200 custom-built species distribution models and environmental metrics via estimates of bioclimatic variables associated with individual moth observations. To access community science data, we developed a novel method for measuring wing lengths from un-scaled photos. Integrating these data into phylogenetically-informed mixed models, we find a positive association between bat predation pressure and moth tail length and body size, and a negative association between environmental factors and these morphological traits. Regions with more insectivorous bats and more consistent temperatures tend to host longer-tailed moths. Our study provides insight into tradeoffs between biotic selective pressures and abiotic constraints that shape elaborate traits across the tree-of-life.
Spatiotemporal control of cell ablation using Ronidazole with Nitroreductase inDrosophila
Authors: Teeters Gary , Cucolo Christina E. , Kasar Sagar N. , Worley Melanie I. , Siegrist Sarah E. 
Published: May 2024

AbstractThe ability to induce cell death in a controlled stereotypic manner has led to the discovery of evolutionary conserved molecules and signaling pathways necessary for tissue growth, repair, and regeneration. Here we report the development of a new method to genetically induce cell death in a controlled stereotypic manner inDrosophila. This method has advantages over other current methods and relies on expression of theE. colienzyme Nitroreductase (NTR) with exogenous application of the nitroimidazole prodrug, Ronidazole. NTR expression is controlled spatially using the GAL4/UAS system while temporal control of cell death is achieved through timed feeding of Ronidazole supplied in the diet. In cells expressing NTR, Ronidazole is converted to a toxic substance inducing DNA damage and cell death. Caspase cell death is achieved in a range of NTR-expressing cell types with Ronidazole feeding, including epithelial, neurons, and glia. Removing Ronidazole from the diet restores cell death to normal unperturbed levels. Unlike other genetic ablation methods, temporal control is achieved through feeding not temperature, circumventing developmental complications associated with temperature changes. Ronidazole-NTR also requires only two transgenes, a GAL4 driver andUAS-NTR, which is generated as a GFP-NTR fusion allowing for easy setup of large-scale screening ofUAS-RNAilines. Altogether, Ronidazole-NTR provides a new streamlined method for inducing cell death inDrosophilawith temperature-independent ON/OFF control.
Bispecific antibodies with broad neutralization potency against SARS-CoV-2 variants of concern
Authors: Rubio Adonis A. , Baharani Viren A. , Dadonaite Bernadeta , Parada Megan , Abernathy Morgan E. , Wang Zijun , Lee Yu E. , Eso Michael R. , Phung Jennie , Ramos Israel , Chen Teresia , Nesr Gina El , Bloom Jesse D. , Bieniasz Paul D. , Nussenzweig Michel C. , Barnes Christopher O. 
Published: May 2024

AbstractThe ongoing emergence of SARS-CoV-2 variants of concern (VOCs) that reduce the effectiveness of antibody therapeutics necessitates development of next-generation antibody modalities that are resilient to viral evolution. Here, we characterized N-terminal domain (NTD) and receptor binding domain (RBD)-specific monoclonal antibodies previously isolated from COVID-19 convalescent donors for their activity against emergent SARS-CoV-2 VOCs. Among these, the NTD-specific antibody C1596 displayed the greatest breadth of binding to VOCs, with cryo-EM structural analysis revealing recognition of a distinct NTD epitope outside of the site i antigenic supersite. Given C1596’s favorable binding profile, we designed a series of bispecific antibodies (bsAbs) termed CoV2-biRNs, that featured both NTD and RBD specificities. Notably, two of the C1596-inclusive bsAbs, CoV2-biRN5 and CoV2-biRN7, retained potentin vitroneutralization activity against all Omicron variants tested, including XBB.1.5, EG.5.1, and BA.2.86, contrasting the diminished potency of parental antibodies delivered as monotherapies or as a cocktail. Furthermore, prophylactic delivery of CoV2-biRN5 significantly reduced the viral load within the lungs of K18-hACE2 mice following challenge with SARS-CoV-2 XBB.1.5. In conclusion, our NTD-RBD bsAbs offer promising potential for the design of resilient, next-generation antibody therapeutics against SARS-CoV-2 VOCs.One Sentence SummaryBispecific antibodies with a highly cross-reactive NTD antibody demonstrate resilience to SARS-CoV-2 variants of concern.
Rapid radiation of a plant lineage sheds light on the assembly of dry valley biomes
Authors: Chen Ya-Ping , Sunojkumar Purayidathkandy , Spicer Robert A. , Hodel Richard G.J. , Soltis Douglas E. , Soltis Pamela S. , Paton Alan J. , Sun Miao , Drew Bryan T. , Xiang Chun-Lei 
Published: May 2024

AbstractSouthwest China is characterized by high plateaus, large mountain systems, and deeply incised dry valleys formed by major rivers and their tributaries. Despite the considerable attention given to alpine plant radiations in this region, the timing and mode of the diversification of the numerous plant lineages in the dry valley habitat remains unknown. To address this knowledge gap, we investigate the macroevolution ofIsodon(Lamiaceae), a lineage commonly distributed in the dry valleys in southwest China and wetter areas of Asia and Africa. We reconstructed a robust phylogeny encompassing nearly 90% of the approximately 140 extantIsodonspecies using transcriptome and genome-resequencing data. Our results suggest a rapid radiation ofIsodonduring the Pliocene that coincided with a habit shift from herbs to shrubs and a habitat shift from humid areas to dry valleys. The shrubby growth form likely acted as a preadaptation allowing for the movement ofIsodonspecies into these valleys. Ecological analysis highlighted aridity and precipitation as key factors influencing the niche preferences of different growth forms and species richness ofIsodon. Integrating our results with insights from tectonic movements in the Tibetan Plateau and adjacent regions, we infer that the interplay between topography and the evolution of the East Asian monsoon since the middle Miocene likely contributed to the formation of the dry valley biome in southwest China. This study enhances our understanding of evolutionary dynamics and ecological drivers shaping the distinctive flora of this region.