bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian dynamics of the Zbtb14 protein in the ventral hippocampus are disrupted in epileptic mice
Authors: Güntan İlke , Ghestem Antoine , Nazaruk Kinga , Nizińska Karolina , Olszewski Maciej , Nowicka Dorota , Bernard Christophe , Łukasiuk Katarzyna 
Published: March 2024

AbstractOur previousin silicodata indicated an overrepresentation of the ZF5 motif in the promoters of genes in which circadian oscillations are altered in the ventral hippocampus in the pilocarpine model of temporal lobe epilepsy in mice. In this study, we test the hypothesis that the Zbtb14 protein oscillates in the hippocampus in a circadian manner and that this oscillation is disrupted by epilepsy.We found that Zbtb14 immunostaining is present in the cytoplasm and cell nuclei. Western blot data indicate that the cytoplasmic and nuclear levels of Zbtb14 protein oscillate, but the phase is shifted. The densities of the Zbtb14-immunopositive express circadian dynamics in the ventral hilus and Ca3 but not in the dorsal hilus, Ca3, or the somatosensory cortex. In the pilocarpine model of epilepsy increase in the level of Zbtb14 protein was found at 11 PM, but not at 3 PM compared to controls. Finally,in silicoanalysis revealed the presence of the ZF5 motif in the promoters of 21 out of 24 genes down-regulated by epileptiform dischargesin vitro, many of which are involved in neuronal plasticity. Our data suggest that Zbtb14 may be involved in the circadian dynamic of seizure regulation or brain response to seizure rhythmicity.Highlightsthe Zbtb14 protein is expressed in neurons in the mouse brain;Zbtb14 protein levels oscillate through the circadian cycle in the ventral hippocampus but not in the dorsal hippocampus;the oscillations of the Zbtb14 protein occur in both the cytoplasm and nucleus but in a different temporal pattern;the circadian dynamics of the Zbtb14 protein are perturbed in epilepsy in anin vivomodel of epilepsy;numerous genes that are downregulated in thein vitromodel of epileptiform discharges have a ZF5 motif in their promoters
HyperTraPS-CT: Inference and prediction for accumulation pathways with flexible data and model structures
Authors: Aga Olav N. L. , Brun Morten , Dauda Kazeem A. , Diaz-Uriarte Ramon , Giannakis Konstantinos , Johnston Iain G. 
Published: March 2024

AbstractAccumulation processes, where many potentially coupled features are acquired over time, occur throughout the sciences, from evolutionary biology to disease progression, and particularly in the study of cancer progression. Existing methods for learning the dynamics of such systems typically assume limited (often pairwise) relationships between feature subsets, cross-sectional or untimed observations, small feature sets, or discrete orderings of events. Here we introduce HyperTraPS-CT (Hypercubic Transition Path Sampling in Continuous Time) to compute posterior distributions on continuous-time dynamics of many, arbitrarily coupled, traits in unrestricted state spaces, accounting for uncertainty in observations and their timings. We demonstrate the capacity of HyperTraPS-CT to deal with cross-sectional, longitudinal, and phylogenetic data, which may have no, uncertain, or precisely specified sampling times. HyperTraPS-CT allows positive and negative interactions between arbitrary subsets of features (not limited to pairwise interactions), supporting Bayesian and maximum-likelihood inference approaches to identify these interactions, consequent pathways, and predictions of future and unobserved features. We also introduce a range of visualisations for the inferred outputs of these processes and demonstrate model selection and regularisation for feature interactions. We apply this approach to case studies on the accumulation of mutations in cancer progression and the acquisition of anti-microbial resistance genes in tuberculosis, demonstrating its flexibility and capacity to produce predictions aligned with applied priorities.
Hemozoin induces Malaria via activation of DNA damage, p38 MAPK and Neurodegenerative Pathways in Human iPSC-derived Neuronal Model of Cerebral Malaria
Authors: Pranty Abida lslam , Szepanowski Leon-Phillip , Wruck Wasco , Karikari Akua Afriyie , Adjaye James 
Published: March 2024

AbstractMalaria caused byPlasmodium falciparuminfection results in severe complications including cerebral malaria (CM), in which approximately 30% of patients end up with neurological sequelae. Sparse in vitro cell culture-based experimental models which recapitulate the molecular basis of CM in humans has impeded progress in our understanding of its etiology. This study employed healthy human induced pluripotent stem cells (iPSCs) derived neuronal cultures stimulated with hemozoin (HMZ)-the malarial toxin as a model for CM. Secretome, qRT-PCR, Metascape, and KEGG pathway analyses were conducted to assess elevated proteins, genes, and pathways. Neuronal cultures treated with HMZ showed enhanced secretion of interferon-gamma (IFN-γ), interleukin (IL)1-beta (IL-1β), IL-8 and IL-16. Enrichment analysis revealed malaria, positive regulation of cytokine production and positive regulation of mitogen-activated protein kinase (MAPK) cascade which confirm inflammatory response to HMZ exposure. KEGG assessment revealed up-regulation of malaria, MAPK and neurodegenerative diseases-associated pathways which corroborates findings from previous studies. Additionally, HMZ induced DNA damage in neurons. This study has unveiled that exposure of neuronal cultures to HMZ, activates molecules and pathways similar to that observed in CM and neurodegenerative diseases. Furthermore, our model is an alternative to rodent experimental models of CM.
A high resolution model of the grapevine leaf morphospace predicts synthetic leaves
Authors: Chitwood Daniel H. , Torres-Lomas Efrain , Hadi Ebi S. , Peterson Wolfgang L. G. , Fischer Mirjam F. , Rogers Sydney E. , He Chuan , Acierno Michael G. F. , Azumaya Shintaro , Benjamin Seth Wayne , Chalise Devendra Prasad , Chess Ellice E. , Engelsma Alex J. , Fu Qiuyi , Jaikham Jirapa , Knight Bridget M. , Kodjak Nikita S. , Lengyel Adazsofia , Muñoz Brenda L. , Patterson Justin T. , Rincon Sundara I. , Schumann Francis L. , Shi Yujie , Smith Charlie C. , Clair Mallory K. St. , Sweeney Carly S. , Whitaker Patrick , Wu James , Diaz-Garcia Luis 
Published: March 2024

SummaryGrapevine leaves are a model morphometric system. Sampling over ten thousand leaves using dozens of landmarks, the genetic, developmental, and environmental basis of leaf shape has been studied and a morphospace for the genusVitispredicted. Yet, these representations of leaf shape fail to capture the exquisite features of leaves at high resolution.We measure the shapes of 139 grapevine leaves using 1672 pseudo-landmarks derived from 90 homologous landmarks with Procrustean approaches. From hand traces of the vasculature and blade, we have derived a method to automatically detect landmarks and place pseudo-landmarks that results in a high-resolution representation of grapevine leaf shape. Using polynomial models, we create continuous representations of leaf development in 10Vitisspp.We visualize a high-resolution morphospace in which genetic and developmental sources of leaf shape variance are orthogonal to each other. Using classifiers,V. vinifera, Vitisspp., rootstock and dissected leaf varieties as well as developmental stages are accurately predicted. Theoretical eigenleaf representations sampled from across the morphospace that we call synthetic leaves can be classified using models.By predicting a high-resolution morphospace and delimiting the boundaries of leaf shapes that can plausibly be produced within the genusVitis, we can sample synthetic leaves with realistic qualities. From an ampelographic perspective, larger numbers of leaves sampled at lower resolution can be projected onto this high-resolution space; or, synthetic leaves can be used to increase the robustness and accuracy of machine learning classifiers.Societal Impact StatementGrapevine leaves are emblematic of the strong visual associations people make with plants. At a glance, leaf shape is immediately recognizable, and it is because of this reason it is used to distinguish grape varieties. In an era of computationally-enabled, machine learning-derived representations of reality, we can revisit how we view and use the shapes and forms that plants display to understand our relationship with them. Using computational approaches combined with time-honored methods, we can predict theoretical leaves that are possible to understand the genetics, development, and environmental responses of plants in new ways.
Requirement of a Wnt5A-Microbiota Axis in the Maintenance of Gut B Cell Repertoire and Protection from Infection
Authors: Sengupta Soham , Sen Malini 
Published: March 2024

AbstractWe investigated the influence of a Wnt5A-gut microbiota axis on gut B cell repertoire and protection from infection, having previously demonstrated that Wnt5A in association with gut commensals help shape gut T cell repertoire. Accordingly, Wnt5A heterozygous mice, which express less than wild type level of Wnt5A, and their isolated Peyer’s patches (PP), were studied in comparison with the wild type counterparts. The percentages of IgM and IgA expressing B cells were quite similar in the PP of both sets of mice. However, the PP of the Wnt5A heterozygous mice harbored significantly higher than wild type levels of microbiota bound B cell secreted IgA (sIgA), indicating the prevalence of a microbial population therein, that is significantly altered from that of wild type. Additionally, the percentage of PP IgG1 expressing B cells was appreciably depressed in the Wnt5A heterozygous mice in comparison to wild type. Wnt5A heterozygous mice, furthermore, exhibited notably higher than the wild type levels of morbidity and mortality following infection withSalmonella enterica, a common gut pathogen. Difference in morbidity/mortality correlated with considerable disparity between the PP-B cell repertoires of theSalmonellainfected Wnt5A heterozygous and wild type mice, the percentage of IgG1 expressing B1b cells in the PP of heterozygous mice remaining significantly low as compared to wild type. Overall, these results suggest that a gut Wnt5A-microbiota axis is intrinsically associated with the maintenance of gut B cell repertoire and protection from infection.ImportanceAlthough it is well accepted that B cells and microbiota are required for protection from infection and preservation of gut health, a lot remains unknown about how the optimum B cell repertoire and microbiota are maintained in the gut. The importance of this study lies in the fact that it unveils a potential role of a growth factor termed Wnt5A in the safeguarding of the gut B cell population and microbiota, thereby protecting the gut from the deleterious effect of infections by common pathogens. Documentation of the involvement of a Wnt5A-microbiota axis in the shaping of a protective gut B cell repertoire, furthermore, opens up new avenues of investigations for understanding gut disorders related to microbial dysbiosis and B cell homeostasis that till date, are considered incurable.
Interspecific trait differences drive plant community responses on serpentine soils
Authors: Delhaye Guillaume , Dimitrakopoulos Panayiotis G. , Adamidis George C. 
Published: March 2024

AbstractSerpentine ecosystems are characterized by multiple environmental stressors such as high levels of trace metals such as nickel (Ni), low availability of macronutrients and low water retention. These harsh environmental conditions exert a strong selective force on the vegetation, but their effect on the functional trait composition of the communities remains unknown.In 26 plots on four serpentine sites on Lesbos Island (Greece), we measured six leaf functional traits related to resource acquisition and stress resistance on the 20 most abundant plant species. We quantified the proportion of variance explained by inter- and intraspecific traits difference and tested if individual species show changes in trait values explained by soil Ni content. We investigated the selective value and the community level changes for each trait along the natural soil Ni gradient using a species multilevel model approach and functional diversity analyses. We also tested the role of the abundant serpentine endemicOdontarrhena lesbiacain driving these patterns.Intraspecific variation explained by soil Ni content is smaller than 2%, with most of the variance being explained by interspecific differences in trait values and most species do not show significant changes in trait values. At the community level, leaf thickness is the only trait driving an increase in species abundance along the gradient. Functional diversity analyses suggest a shift towards a stress tolerance syndrome (thick leaves with low SLA values) on Ni rich soils, but an increase in the diversity of these traits. However, these patterns are driven by the increasing abundance ofO. lesbiaca. When this species is excluded, there is an increase in the community mean leaf area and SLA, suggesting that the community does not respond to metallic stress with classical stress syndromes.Synthesis.Intraspecific variation in leaf trait responds little to soil metal toxicity. Endemic species harbour original trait values compared to species with broad distribution which should justify their conservation as a priority.
Repeatability of an extended phenotype: potential causes and consequences of nest variation in the Northern House Wren (Troglodytes aedon aedon)
Authors: Carr Chandler E. G. , Swanson Zoë M. , Reichard Dustin G. 
Published: March 2024

ABSTRACTLAY SUMMARYRepeatability of construction behaviors in the wild is understudiedHouse Wrens are a cavity-nesting songbirdHouse Wren nests are highly variable in their morphologyFemale House Wrens are repeatable in cup composition, but not nest dimensionsThe dimensions of the nest are built to match the dimensions of the cavityHouse Wren nests are unrelated to nestling survival or female conditionFemale preferences for nest building may explain nest variationConstruction behavior is an aspect of the extended phenotype that allows organisms to build structures that alter their environments in potentially beneficial ways. Although individuals vary in the expression of this extended phenotype (e.g., structure morphology), the repeatability of construction behaviors remain understudied, especially among free-living populations. Many oviparous taxa construct nests, making them of particular interest because variation in nest architecture may directly affect fitness. Using a free-living, cavity-nesting songbird, the Northern House Wren (Troglodytes aedon aedon), as our model, we estimated the contribution of the primary builder (the female) to nest variability by measuring the repeatability of nest morphology between successive clutches. We further examined whether nest morphology was related to the dimensions of the nesting cavity, breeding date, or nest success. We found the composition of the cup lining to be a highly repeatable behavior for the nesting female, although the size and composition of the structural platform appeared more related to the dimensions of the cavity. Nest morphology remained variable throughout the breeding season, showing no significant correlations with breeding date, and it was unrelated to clutch size or offspring survival. Our study suggests that variation in construction behavior is likely the product of multiple factors including the preferences of the builder and physical constraints. The absence of any clear links between construction behavior and fitness indicates that nest morphology is not under strong selection. As a result, diverse female building preferences may explain the extreme among-individual variation in nest structure in this species.
Local FK506 delivery induces osteogenesis inin vivorat bone defect and rabbit spine fusion models
Authors: Harrer Julia Andraca , Fulton Travis M. , Sangadala Sreedhara , Kaiser Jarred , Devereaux Emily J. , Oliver Colleen , Presciutti Steven M. , Boden Scott D. , Willett Nick J. 
Published: March 2024

AbstractBone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and significantly increase surgical costs, adding to patients’ already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 potentiated the effect of low dose BMP-2 to enhance osteogenic differentiation and mineralization of hMSCsin vitro. Standalone treatment with FK506 delivered on a collagen sponge, produced consistent bone bridging of a rat critically-sized femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challengingin vivomodels, and indicate FK506 can be utilized either as a standalone treatment or in conjunction with rhBMP to treat a variety of spine disorders.Graphical Abstract
Bayesian Optimization of Neurostimulation (BOONStim)
Authors: Oliver Lindsay D. , Jeyachandra Jerrold , Dickie Erin W. , Hawco Colin , Mansour Salim , Hare Stephanie M. , Buchanan Robert W. , Malhotra Anil K. , Blumberger Daniel M. , Deng Zhi-De , Voineskos Aristotle N. 
Published: March 2024

AbstractBackgroundTranscranial magnetic stimulation (TMS) treatment response is influenced by individual variability in brain structure and function. Sophisticated, user-friendly approaches, incorporating both established functional magnetic resonance imaging (fMRI) and TMS simulation tools, to identify TMS targets are needed.ObjectiveThe current study presents the development and validation of the Bayesian Optimization of Neuro-Stimulation (BOONStim) pipeline.MethodsBOONStim uses Bayesian optimization for individualized TMS targeting, automating interoperability between surface-based fMRI analytic tools and TMS electric field modeling. BOONStim’s Bayesian optimization performance was evaluated in a sample dataset (N=10) using standard circular and functional connectivity-defined targets, and compared to densely sampled grid optimization.ResultsBayesian optimization converged to similar levels of total electric field stimulation across targets in under 30 iterations, converging within 5% error of the maxima detected by grid optimization, and requiring less time.ConclusionsBOONStim is a scalable and configurable user-friendly pipeline for individualized TMS targeting with quick turnaround.
Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy
Authors: Yazdimamaghani Mostafa , Kolupaev Oleg V. , Lim Chaemin , Hwang Duhyeong , Laurie Sonia J. , Perou Charles M. , Kabanov Alexander V. , Serody Jonathan S. 
Published: March 2024

AbstractInfiltration of immunosuppressive cells into the breast tumor microenvironment (TME) is associated with suppressed effector T cell (Teff) responses, accelerated tumor growth, and poor clinical outcomes. Previous studies from our group and others identified infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) as critical contributors to immune dysfunction in the orthotopic triple-negative breast cancer (TNBC) tumor model limiting the efficacy of adoptive cellular therapy. However, approaches to target these cells specifically in the TME are currently lacking. To overcome this barrier, polymeric micelles nanoparticles (PMNPs) were used for co-delivery of small molecule drugs activating Toll-like receptors 7 and 8 (TLR7/8) and inhibiting PI3K delta. The immunomodulation of the TME by TLR7/8 agonist and PI3K inhibitor altered macrophage polarization, reduced MDSC accumulation and selectively decreased tissue-resident Tregs in the TME, while enhancing the T and B cell adaptive immune response. PMNPs significantly enhanced the anti-tumor activity of local radiation therapy (RT) in mice bearing orthotopic TNBC tumors compared to RT alone. Taken together, these data demonstrate that RT combined with a nanoformulated immunostimulant restructured the TME and has promising potential for future translation combined with RT for patients with TNBC.
Effective connectivity predicts distributed neural coding of perceptual decision confidence, uncertainty and speed
Authors: Asadpour Abdoreza , Wong-Lin KongFatt 
Published: March 2024

AbstractDecision-making is often accompanied by a level of confidence regarding the accuracy of one’s decision. Previous studies have indicated neural activity associated with perceptual decision confidence during sensory stimulus presentation. Choice-based reaction time (RT) has been suggested as an indirect but more objective measure of decision confidence – generally faster RT for higher confidence. However, it is unclear whether choice confidence and RT are mediated by distinct neural pathways, and whether their neural correlates are encoded nonlinearly. Within a perceptual decision-making task, we applied fMRI-informed EEG-based effective connectivity analysis via dynamic causal modelling (DCM) on event-related potentials and found the frontoparietal network for fast-vs-slow RT condition to be different from that of high-vs-low confidence rating condition. Furthermore, trial-by-trial DCM analysis predicted cortical layer-based, distributed and nonlinear coding of RT, confidence or uncertainty. Collectively, our study suggests that decision confidence and speed are instantiated by different dynamical networks distributed across cortical layers.