bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of pathogen sexual reproduction on the evolutionary and epidemiological control provided by deployment strategies for two major resistance genes in agricultural landscapes
Authors: Zaffaroni Marta , Rimbaud Loup , Rey Jean-François , Papaïx Julien , Fabre Frédéric 
Published: February 2023

SummaryResistant cultivars are of value for protecting crops from disease, but can be rapidly overcome by pathogens. Several strategies have been proposed to delay pathogen adaptation (evolutionary control), while maintaining effective protection (epidemiological control). Resistance genes can bei) combined in the same cultivar (pyramiding),ii) deployed in different cultivars sown in the same field (mixtures) or in different fields (mosaics), oriii) alternated over time (rotations). The outcomes of these strategies have been investigated principally in pathogens displaying pure clonal reproduction, but sexual reproduction may promote the emergence of superpathogens adapted to all the resistance genes deployed.We improved the spatially explicit stochastic modellandsepito include pathogen sexual reproduction, and then investigate the effect of sexual reproduction on evolutionary and epidemiological outcomes across deployment strategies for two major resistance genes.Sexual reproduction only favours the establishment of a superpathogen when single mutant pathogens are present together at a sufficiently high frequency, as in mosaic and mixture strategies.We concluded that, although sexual reproduction may promote the establishment of a superpathogen, it did not affect the optimal strategy recommendations for a wide range of mutation probabilities, associated fitness costs, and landscape organisations (notably the cropping ratio of resistant fields).
Thermal conditioning of quail embryos has transgenerational and reversible long-term effects
Authors: Carvalho Anaïs Vitorino , Hennequet-Antier Christelle , Rouger Romuald , Delaveau Joël , Bordeau Thierry , Crochet Sabine , Couroussé Nathalie , Pitel Frederique , Collin Anne , Coustham Vincent 
Published: February 2023

AbstractIn the current context of global warming, thermal manipulation of avian embryos has received increasing attention as a strategy to promote heat tolerance in avian species by simply increasing the egg incubation temperature. However, because of their likely epigenetic origin, thermal manipulation effects may last more than one generation with consequences for the poultry industry. We found that thermal manipulation repeated during 4 generations had an effect on hatchability, body weight, and weight of eggs laid in Japanese quails, with some effects increasing in importance over generations. Moreover, we show that the effects on body weight and egg weight can be transmitted transgenerationally, suggesting non-genetic inheritance mechanisms. This hypothesis is reinforced by the observed reversion of the effect on growth after five unexposed generations. Interestingly, we demonstrate a non-transgenerational effect of thermal manipulation on heat tolerance few days after hatch. In conclusion, our multigenerational study suggests a quantitative, transgenerational and reversible effect of thermal manipulation.
Development of attention-based robust deep learning model for tongue diagnosis by smartphone
Authors: Ma Changzheng , Gao Chaofei , Hou Siyu , Li Shao 
Published: February 2023

AbstractCompared with tongue diagnosis using tongue image analyzers, tongue diagnosis by smartphone has great advantages in convenience and cost for universal health monitoring, but its accuracy is affected by the shooting conditions of smartphones. Developing deep learning models with high accuracy and robustness to changes in the shooting environment for tongue diagnosis by smartphone and determining the influence of environmental changes on accuracy are necessary. In our study, a dataset of 9003 images was constructed after image pre-processing and labeling. Next, we developed an attention-based deep learning model (Deep Tongue) for 8 subtasks of tongue diagnosis, including the spotted tongue, teeth-marked tongue, and fissure tongue et al, which the average AUC of was 0.90, higher than the baseline model (ResNet50) by 0.10. Finally, we analyzed the objective reasons, the brightness of the environment and the hue of images, affecting the accuracy of tongue diagnosis by smartphone through a consistency experiment of direct subject inspection and tongue image inspection. Finally, we determined the influence of environmental changes on accuracy to quantify the robustness of the Deep Tongue model through simulation experiments. Overall, the Deep Tongue model achieved a higher and more stable classification accuracy of seven tongue diagnosis tasks in the complex shooting environment of the smartphone, and the classification of tongue coating (yellow/white) was found to be sensitive to the hue of the images and therefore unreliable without stricter shooting conditions and color correction.
Cognitive control activity is enhanced by single pulse transcranial magnetic stimulation over prefrontal and premotor areas
Authors: Cespón Jesús , Pellicciari Maria Concetta , Miniussi Carlo 
Published: February 2023

ABSTRACTCognitive control, which includes a set of processes to implement goal directed actions and flexible behaviour, is related to a set of brain areas comprising prefrontal, premotor, and parietal cortex. However, the functional relationships between these areas and the neural correlates underlying the specific cognitive processes linked to cognitive control (e.g., inhibition and working memory update) are still unclear. In the present study, participants performed a spatial cognitive control task (i.e., a Simon task) during a transcranial magnetic stimulation electroencephalogram (TMS-EEG) co-registration. In different blocks of the task, single pulse TMS was applied over the left prefrontal, premotor, and parietal regions (a sham TMS condition was also included) at 180ms after the stimulus onset. Behavioural differences between the four TMS conditions were not observed. Accordingly, activity to inhibit the response toward the attended location was not modulated by TMS, as indexed by the contralateral central negativity (N2cc), even if TMS over parietal regions accelerated the visuospatial processing, as evidenced by faster contralateral posterior negativity (N2pc). Importantly, we observed larger P300 amplitude when delivering TMS over prefrontal and premotor cortex compared to the sham condition. These results suggest that TMS applied over the left prefrontal and premotor regions could enhances working memory processes linked to switch-and-update of the stimulus-response binding and align with the existence of prefrontal-premotor connections.
Erasable Hippocampal Neural Signatures Predict Memory Discrimination
Authors: Kinsky Nathaniel R. , Orlin Daniel J. , Ruesch Evan A. , Kim Brian , Coello Siria , Diba Kamran , Ramirez Steve 
Published: February 2023

SummaryMemories involving the hippocampus can take several days to consolidate, challenging efforts to uncover the neuronal signatures underlying this process. Using calcium imaging in freely moving mice, we tracked the hippocampal dynamics underlying memory formation across a ten-day contextual fear conditioning (CFC) task. Following learning, context-specific place field remapping correlated with memory performance. To causally test whether these hippocampal dynamics support memory consolidation, we induced amnesia in a group of mice by pharmacologically blocking protein synthesis immediately following learning. We found that halting protein synthesis following learning paradoxically accelerated cell turnover and also arrested learning-related remapping, paralleling the absence of remapping observed in untreated mice that exhibited poor memory expression. Finally, coordinated neural activity that emerged following learning was dependent on intact protein synthesis and predicted memory-related freezing behavior. We conclude that context-specific place field remapping and the development of coordinated ensemble activity require protein synthesis and underlie contextual fear memory consolidation.
Paired single-cell multi-omics data integration with Mowgli
Authors: Huizing Geert-Jan , Deutschmann Ina Maria , Peyré Gabriel , Cantini Laura 
Published: February 2023

AbstractThe profiling of multiple molecular layers from the same set of cells has recently become possible. There is thus a growing need for multi-view learning methods able to jointly analyze these data. We here present Multi-Omics Wasserstein inteGrative anaLysIs (Mowgli), a novel method for the integration of paired multi-omics data with any type and number of omics. Of note, Mowgli combines integrative Nonnegative Matrix Factorization (NMF) and Optimal Transport (OT), enhancing at the same time the clustering performance and interpretability of integrative NMF. We apply Mowgli to multiple paired single-cell multi-omics data profiled with 10X Multiome, CITE-seq and TEA-seq. Our in depth benchmark demonstrates that Mowgli’s performance is competitive with the state-of-the-art in cell clustering and superior to the state-of-the-art once considering biological interpretability. Mowgli is implemented as a Python package seamlessly integrated within the scverse ecosystem and it is available athttp://github.com/cantinilab/mowgli.
Bayesian optimization for design of multiscale biological circuits
Authors: Merzbacher Charlotte , Mac Aodha Oisin , Oyarzún Diego A. 
Published: February 2023

AbstractRecent advances in synthetic biology have enabled the construction of molecular circuits that operate across multiple scales of cellular organization, such as gene regulation, signalling pathways and cellular metabolism. Computational optimization can effectively aid the design process, but current methods are generally unsuited for systems with multiple temporal or concentration scales, as these are slow to simulate due to their numerical stiffness. Here, we present a machine learning method for the efficient optimization of biological circuits across scales. The method relies on Bayesian Optimization, a technique commonly used to fine-tune deep neural networks, to learn the shape of a performance landscape and iteratively navigate the design space towards an optimal circuit. This strategy allows the joint optimization of both circuit architecture and parameters, and hence provides a feasible approach to solve a highly non-convex optimization problem in a mixed-integer input space. We illustrate the applicability of the method on several gene circuits for controlling biosynthetic pathways with strong nonlinearities, multiple interacting scales, and using various performance objectives. The method efficiently handles large multiscale problems and enables parametric sweeps to assess circuit robustness to perturbations, serving as an efficientin silicoscreening method prior to experimental implementation.
Finding phylogeny-aware and biologically meaningful averages of metagenomic samples:L2UniFrac
Authors: Wei Wei , Millward Andrew , Koslicki David 
Published: February 2023

AbstractMetagenomic samples have high spatiotemporal variability. Hence, it is useful to summarize and characterize the microbial makeup of a given environment in a way that is biologically reasonable and interpretable. The UniFrac metric has been a robust and widely-used metric for measuring the variability between metagenomic samples. We propose that the characterization of metagenomic environments can be achieved by finding the average, a.k.a. the barycenter, among the samples with respect to the UniFrac distance. However, it is possible that such a UniFrac-average includes negative entries, making it no longer a valid representation of a metagenomic community. To overcome this intrinsic issue, we propose a special version of the UniFrac metric, termedL2UniFrac, which inherits the phylogenetic nature of the traditional UniFrac and with respect to which one can easily compute the average, producing biologically meaningful environment-specific “representative samples”. We demonstrate the usefulness of such representative samples as well as the extended usage ofL2UniFrac in efficient clustering of metagenomic samples, and provide mathematical characterizations and proofs to the desired properties ofL2UniFrac. A prototype implementation is provided at:https://github.com/KoslickiLab/L2-UniFrac.git.
Bioinformatic identification of ClpI, a class of Clp unfoldase in Actinomycetota
Authors: Jiang Jialiu , Schmitz Karl R. 
Published: February 2023

ABSTRACTAll clades of bacteria possess Hsp100/Clp family unfoldase enzymes that contribute to aspects of protein quality control. In Actinomycetota, these include ClpB, which functions as an independent chaperone and disaggregase, and ClpC, which cooperates with the ClpP1P2 peptidase to carry out regulated proteolysis of client proteins. We initially sought to algorithmically catalog Clp unfoldase orthologs from Actinomycetota into ClpB and ClpC categories. In the process, we uncovered a phylogenetically distinct third group of double-ringed Clp enzymes, which we term ClpI. ClpI enzymes are architecturally similar to ClpB and ClpC, with intact ATPase modules and motifs associated with substrate unfolding and translation. While ClpI possess an M-domain similar in length to that of ClpC, their N-terminal domain is more variable than the strongly conserved N-terminal domain of ClpC. Surprisingly, we identified separate sets of ClpI sequences that possess or lack the LGF-motifs required for stable assembly with ClpP1P2. In species where they occur, we suggest that ClpI enzymes provides additional pathways and points of regulatory control over protein quality control programs, supplementing the conserved roles of ClpB and ClpC.
Xenopus laevislack the critical sperm factor PLCζ
Authors: Bainbridge Rachel E. , Rosenbaum Joel C. , Sau Paushaly , Carlson Anne E. 
Published: February 2023

AbstractFertilization of eggs from the African clawed frogXenopus laevisis characterized by an increase in cytosolic calcium, a phenomenon that is also observed in other vertebrates such as mammals and birds. During fertilization in mammals and birds, the transfer of the soluble PLCζ from sperm into the egg is thought to trigger the release of calcium from the endoplasmic reticulum (ER). Injecting sperm extracts into eggs reproduces this effect, reinforcing the hypothesis that a sperm factor is responsible for calcium release and egg activation. Remarkably, this occurs even when sperm extracts fromX. laevisare injected into mouse eggs, suggesting that mammals andX. laevisshare a sperm factor. However,X. laevislacks an annotatedPLCZ1gene, which encodes the PLCζ enzyme. In this study, we attempted to determine whether sperm fromX. laevisexpress an unannotatedPLCZ1ortholog. We identifiedPLCZ1orthologs in 11 amphibian species, including 5 that had not been previously characterized, but did not find any in eitherX. laevisor the closely relatedXenopus tropicalis. Additionally, we performed RNA sequencing on testes obtained from adultX. laevismales and did not identify potential PLCZ1 orthologs in our dataset or in previously collected ones. These findings suggest that PLCZ1 may have been lost in theXenopuslineage and raise the question of how fertilization triggers calcium release and egg activation in these species.
Rosuvastatin-Eluting Gold Nanoparticle-Loaded Perivascular Implantable Wrap for Enhanced Arteriovenous Fistula Maturation in a Murine Model
Authors: Klusman Carleigh , Martin Benjamin , Perez Joy Vanessa D. , Barcena Allan John R. , Bernardino Marvin R. , San Valentin Erin Marie D. , Damasco Jossana A. , Mundo Huckie C. Del , Court Karem , Godin Biana , Fowlkes Natalie , Bouchard Richard , Cheng Jizhong , Huang Steven Y. , Melancon Marites P. 
Published: February 2023

AbstractBackgroundArteriovenous fistulas (AVFs) are a vital intervention for patients requiring hemodialysis, but they also contribute to overall mortality due to access malfunction. The most common cause of both AVF non-maturation and secondary failure is neointimal hyperplasia (NIH). Absorbable polycaprolactone (PCL) perivascular wraps can address these complications by incorporating drugs to attenuate NIH, such as rosuvastatin (ROSU), and metallic nanoparticles for visualization and device monitoring.ObjectivesThis study aimed to assess the impacts of gold nanoparticle (AuNP) and ROSU-loaded perivascular wraps on vasculature NIH and AVF maturation and patency in a chronic kidney disease rat model.MethodsElectrospun wraps containing combinations of PCL, AuNP, and ROSU were monitored forin vitrodrug elution, nanoparticle release, tensile strength, and cell viability. Perivascular wraps were implanted in chronic kidney disease rats forin vivoultrasound (US) and micro-computed tomography (mCT) imaging. AVF specimens were collected for histological analyses.ResultsNo difference in cell line viability was observed in ROSU-containing grafts.In vitrorelease studies of ROSU and AuNPs correlated with decreasing radiopacity over time onin vivomCT analysis. The mCT study also demonstrated increased radiopacity in AuNP-loaded wraps compared with PCL and control. The addition of ROSU demonstrated decreased US and histologic measurements of NIH.ConclusionsThe reduced NIH seen with ROSU-loading of perivascular wraps suggests a synergistic effect between mechanical support and anti-hyperplasia medication. Furthermore, the addition of AuNPs increased wrap radiopacity. Together, our results show that radiopaque, AuNP-, and ROSU-loaded PCL grafts induce AVF maturation and suppress NIH while facilitating optimal implanted device visualization.
Theoretical understanding of evolutionary dynamics on inhomogeneous networks
Authors: Teimouri Hamid , Khavas Dorsa Sattari , Spaulding Cade , Li Christopher , Kolomeisky Anatoly B. 
Published: February 2023

AbstractEvolution is the main feature of all biological systems that allows populations to change their characteristics over successive generations. A powerful approach to understand evolutionary dynamics is to investigate fixation probabilities and fixation times of novel mutations on networks that mimic biological populations. It is now well established that the structure of such networks can have dramatic effects on evolutionary dynamics. In particular, there are population structures that might amplify the fixation probabilities while simultaneously delaying the fixation events. However, the microscopic origins of such complex evolutionary dynamics remain not well understood. We present here a theoretical investigation of the microscopic mechanisms of mutation fixation processes on inhomogeneous networks. It views evolutionary dynamics as a set of stochastic transitions between discrete states specified by different numbers of mutated cells. By specifically considering star networks, we obtain a comprehensive description of evolutionary dynamics. Our approach allows us to employ physics-inspired free-energy landscape arguments to explain the observed trends in fixation times and fixation probabilities, providing a better microscopic understanding of evolutionary dynamics in complex systems.
Maternal Aggression Driven by the Transient Mobilisation of a Dormant Hormone-Sensitive Circuit
Authors: Stagkourakis Stefanos , Williams Paul , Spigolon Giada , Khanal Shreya , Ziegler Katharina , Heikkinen Laura , Fisone Gilberto , Broberger Christian 
Published: February 2023

AbstractAggression, a sexually dimorphic behaviour, is prevalent in males and typically absent in virgin females. Following parturition, however, the transient expression of aggression in adult female mice protects pups from predators and infanticide by male conspecifics. While maternal hormones are known to elicit nursing, their potential role in maternal aggression remains elusive. Here, we show in mice that a molecularly defined subset of ventral premammillary (PMvDAT) neurons, instrumental for intermale aggression, switch from quiescence to a hyperexcitable state during lactation. We identify that the maternal hormones prolactin and oxytocin excite these cells through actions that include T-type Ca2+channels. Optogenetic manipulation or genetic ablation of PMvDATneurons profoundly affects maternal aggression, while activation of these neurons impairs the expression of non-aggression-related maternal behaviours. This work identifies a monomorphic neural substrate that can incorporate hormonal cues to enable the transient expression of a dormant behavioural program in lactating females.
Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception
Authors: Bustin Katelyn A. , Shishikura Kyosuke , Chen Irene , Lin Zongtao , McKnight Nate , Chang Yuxuan , Wang Xie , Li Jing Jing , Arellano Eric , Pei Liming , Morton Paul D. , Gregus Ann M. , Buczynski Matthew W. , Matthews Megan L. 
Published: February 2023

ABSTRACTChemical platforms that facilitate both the identification and elucidation of new areas for therapeutic development are necessary but lacking. Activity-based protein profiling (ABPP) leverages active site-directed chemical probes as target discovery tools that resolve activity from expression and immediately marry the targets identified with lead compounds for drug design. However, this approach has traditionally focused on predictable and intrinsic enzyme functionality. Here, we applied our activity-based proteomics discovery platform to map non-encoded and post-translationally acquired enzyme functionalities (e.g. cofactors)in vivousing chemical probes that exploit the nucleophilic hydrazine pharmacophores found in a classic antidepressant drug (e.g. phenelzine, Nardil®). We show the probes arein vivoactive and can map proteome-wide tissue-specific target engagement of the drug. In addition to engaging targets (flavoenzymes monoamine oxidase A/B) that are associated with the known therapeutic mechanism as well as several other members of the flavoenzyme family, the probes captured the previously discoveredN-terminal glyoxylyl (Glox) group of Secernin-3 (SCRN3)in vivothrough a divergent mechanism, indicating this functional feature has biochemical activity in the brain. SCRN3 protein is ubiquitously expressed in the brain, yet gene expression is regulated by inflammatory stimuli. In an inflammatory pain mouse model, behavioral assessment of nociception showedScrn3male knockout mice selectively exhibited impaired thermal nociceptive sensitivity. Our study provides a guided workflow to entangle molecular (off)targets and pharmacological mechanisms for therapeutic development.
Histone bivalency regulates the timing of cerebellar granule cell development
Authors: Mätlik Kärt , Govek Eve-Ellen , Paul Matthew R. , Allis C. David , Hatten Mary E. 
Published: February 2023

SummaryDeveloping neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature, multipolar neurons. Here we use RNA-seq and H3K4me3 and H3K27me3 ChIP-seq to analyze how chromatin modifications control gene expression in a specific type of CNS neuron, the mouse cerebellar granule cell (GC). We find that in proliferating GC progenitors (GCPs), H3K4me3/H3K27me3 bivalency is common at neuronal genes and undergoes dynamic changes that correlate with gene expression during migration and circuit formation. Expressing a fluorescent sensor for bivalent H3K4me3 and H3K27me3 domains revealed subnuclear bivalent foci in proliferating GCPs. Inhibiting H3K27 methyltransferases EZH1 and EZH2in vitroand in organotypic cerebellar slices dramatically altered the expression of bivalent genes and induced the downregulation of migration-related genes and upregulation of synaptic genes, inhibited glial-guided migration, and accelerated terminal differentiation. Thus, histone bivalency is required to regulate the timing of the progression from progenitor cells to mature neurons.