bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of an MRI-Derived Head-Neck Finite Element Model
Authors: Bahreinizad Hossein , Chowdhury Suman K. , Paulon Gustavo , Wei Leonardo , Santos Felipe Z. 
Published: February 2023

AbstractPurposeThis study aimed to develop and validate a magnetic resonance imaging (MRI)-based biofidelic head-neck finite element (FE) model comprised of scalp, skull, CSF, brain, dura mater, pia mater, cervical vertebrae, and discs, 14 ligaments, and 42 neck muscles.MethodsWe developed this model using head and neck MRI images of a healthy male participant and by implementing a novel meshing algorithm to create finer hexahedral mesh structures of the brain. The model was validated by replicating four experimental studies: NBDL’s high acceleration profile, Ito’s frontal impact cervical vertebrae study, Alshareef’s brain sonomicrometry study, and Nahum’s impact study.ResultsThe results showed reasonable geometrical fidelity. Our simulated brain displacement and cervical disc strain results were close to their experimental counterparts. The intracranial pressure and brain stress data of our head-only model (excluding neck structures and constraining the base of the skull) were similar to Nahum’s reported results. As neck structures were not considered in Nahum’s study, the FE results of our head-neck model showed slight discrepancies. Notably, the addition of neck structures (head-neck model) reduced brain stress values and uncovered the brain’s intracranial pressure dynamics, which the head-only model failed to capture. Nevertheless, the FE simulation results showed a good agreement (r > 0.97) between the kinematic responses of the head-neck model and NBDL’s experimental results.ConclusionThe developed head-neck model can accurately replicate the experimental results and has the potential to be used as an efficient computational tool for brain and head injury biomechanics research.Statements and DeclarationsThis work was primarily supported by the U.S. Department of Homeland Security (70RSAT21CB0000023). The MRI data acquisition was supported by the Texas Tech Neuroimaging Center.
Temperature and sex shape reproductive barriers in a climate change hotspot
Authors: Gallegos Cristóbal , Hodgins Kathryn A. , Monro Keyne 
Published: February 2023

AbstractClimate change is shifting species ranges and altering reproductive interactions within those ranges, offering closely-related species new scope to mate and potentially hybridize. Predicting hybridization and its outcomes requires assessing the interplay of biological and climatic factors that mediate reproductive barriers across life stages. However, few studies have done so across the range of environments that parents and offspring potentially encounter in nature, as is crucial to understand the environmental sensitivity of reproductive isolation and its fate under climate change. We set out to assess prezygotic and postzygotic reproductive barriers, and their dependence on temperature and sex, in sister species of a marine tubeworm (Galeolaria) from a sentinel region for climate change impacts in southern Australia. We performed reciprocal crosses within- and between-species using replicate populations, and assessed fertility of crosses, survival of embryos, and survival of larvae, at five temperatures spanning the thermal ranges of populations in nature. We found that barriers were weak and independent of temperature at fertilization, but stronger and more temperature-sensitive at larval development, as species diverged in thermal tolerance. Barriers were asymmetric between reciprocal hybrids, moreover, suggesting a complex interplay between thermal adaptation in parental lineages and maternal inheritance of factors (e.g., mitochondria, endosymbionts) that influence hybrid viability across temperatures. Together, our findings provide new insights into the roles of temperature and sex in reproductive barriers across early life stages, and point to shifting strengths of reproductive isolation in future climates.
Completede novoassembly ofTricholoma bakamatsutakechromosomes revealed the structural divergence and differentiation ofTricholomagenomes
Authors: Ichida Hiroyuki , Murata Hitoshi , Hatakeyama Shin , Yamada Akiyoshi , Ohta Akira 
Published: February 2023

SummaryTricholoma bakamatsutake, which is an edible ectomycorrhizal fungus associated with Fagaceae trees, may have diverged before the other species inTricholomasectionCaligata. We generated a highly contiguous whole-genome sequence forT. bakamatsutakeSF-Tf05 isolated in an oak (Quercus salicina) forest in Japan. The assembly of high-fidelity long reads, with a median read length of 12.3 kb, resulted in 13 chromosome-sized contigs comprising 142,068,211 bases with an average GC content of 43.94%. The 13 chromosomes were predicted to encode 11,060 genes. A contig (122,566 bases) presumably containing the whole circular mitochondrial genome was also recovered. The chromosome-wide comparison ofT. bakamatsutakeandT. matsutake(TMA_r1.0) indicated that the basic number of chromosomes (13) was conserved, but the structures of the corresponding chromosomes diverged, with multiple inversions and translocations. Gene conservation and cluster analyses revealed at least three groups inTricholoma. Specifically, allT. bakamatsutakestrains belonged to the “bakamatsutake” clade, which is most proximal to the “caligatum” clade consisting ofT. caligatumandT. fulvocastaneum. The constructed highly contiguous telomere-to-telomere genome sequence of aT. bakamatsutakeisolate will serve as a fundamental resource for future research on the evolution and differentiation ofTricholomaspecies.
Apical extrusion prevents apoptosis from activating an acute inflammatory program in epithelia
Authors: Duszyc Kinga , von Pein Jessica B. , Ramnath Divya , Currin-Ross Denni , Verma Suzie , Lim Fayth , Sweet Matthew J. , Schroder Kate , Yap Alpha S. 
Published: February 2023

AbstractApoptosis is traditionally considered to be an immunologically silent form of cell death. Multiple mechanisms exist to ensure that apoptosis does not stimulate the immune system to cause inflammation or autoimmunity. Against this expectation, we now report epithelia are programmed to provoke, rather than suppress, inflammation in response to apoptosis. We found that an acute inflammatory response led by neutrophils occurs in zebrafish and cell culture when apoptotic epithelial cells cannot be expelled from the monolayer by apical extrusion. This reflects an intrinsic circuit where ATP released from apoptotic cells stimulates epithelial cells in the immediate vicinity to produce IL-8. As the epithelial barrier is compromised when apical extrusion fails, this juxta-apoptotic proinflammatory pathway may represent an early-response mechanism at sites of potential microbial ingress. Conversely, apical extrusion prevents inappropriate epithelial inflammation by physically eliminating apoptotic cells before they can activate this proinflammatory circuit.
Topological Structure of Population Activity in Mouse Visual Cortex Encodes Visual Scene Rotations
Authors: Beshkov Kosio , Einevoll Gaute T. 
Published: February 2023

AbstractThe primary visual cortex is one of the most well understood regions supporting the processing involved in sensory computation. Historically, our understanding of this part of the brain has been driven by describing the features to which individual neurons respond. An alternative approach, which is rapidly becoming a staple in neuroscience, is to study and analyze the geometry and topology of the manifold generated by the neural activity of large populations of neurons.In this work, we introduce a rigorous quantification of the structure of such neural manifolds and address some of the problems the community has to face when conducting topological data analysis on neural data. We do this by analyzing publicly available two-photon optical recordings of primary mouse visual cortex in response to visual stimuli with a densely sampled rotation angle. Since the set of twodimensional rotations lives on a circle, one would hypothesize that they induce a circle-like manifold in neural activity. We confirm this hypothesis by discovering a circle-like neural manifold in the population activity of primary visual cortex. To achieve this, we applied a shortest-path (geodesic) approximation algorithm for computing the persistent homology groups of neural activity in response to visual stimuli. It is important to note that the manifold is highly curved and standard Euclidean approaches failed to recover the correct topology.Furthermore, we identify subpopulations of neurons which generate both circular and non-circular representations of the rotated stimuli, with the circular representations being better for angle decoding. We found that some of these subpopulations, made up of orientationally selective neurons, wrap the original set of rotations on itself which implies that the visual cortex also represents rotations up to 180 degrees.Given these results we propose that population activity can represent the angle of rotation of a visual scene, in analogy with how individual direction-selective neurons represent the angle of direction in local patches of the visual field. Finally, we discuss some of the obstacles to reliably retrieving the truthful topology generated by a neural population.
rtPA Directly Protects Neurons After Intracerebral Hemorrhage through PI3K/AKT/mTOR Pathway
Authors: Jing Jie , Chen Shiling , Wu Xuan , Yang Jingfei , Liu Xia , Wang Jiahui , Wang Jingyi , Li Yunjie , Zhang Ping , Tang Zhouping 
Published: February 2023

AbstractIntracerebral hemorrhage (ICH) is an acute cerebrovascular disease with high disability and mortality rates. Recombinant tissue plasminogen activator (rtPA) is commonly applied for hematoma evacuation in minimally invasive surgery (MIS) after ICH. However, rtPA may contact directly with brain tissue during MIS procedure, which makes it necessary to discuss the safety of rtPA. We found that, in the in vivo ICH model induced by VII-type collagenase, rtPA treatment improved the neurological function of ICH mice, alleviated the pathological damage and decreased the apoptosis and autophagy level of the peri-hematoma tissue. In the in-vitro model of ICH induced by hemin, the administration of rtPA down-regulated neuronal apoptosis, autophagy, and endoplasmic reticulum stress of neurons. Transcriptome sequencing analysis showed that rtPA treatment upregulated the PI3K/AKT/mTOR pathway in neurons, and PI3K inhibitor (LY294002) can reverse the protective effects of rtPA in inhibiting excessive apoptosis, autophagy and ER-stress. Epidermal growth factor receptor inhibitor (AG-1487) reversed the effect of rtPA on PI3K/AKT/mTOR pathway, which might indicate that the EGF domain played an important role in the activation of PI3K/AKT/mTOR pathway.
Distinct regulatory networks control toxin gene expression in elapid and viperid snakes
Authors: Modahl Cassandra M. , Han Summer Xia , van Thiel Jory , Vaz Candida , Dunstan Nathan L. , Frietze Seth , Jackson Timothy N. W. , Mackessy Stephen P. , Kini R. Manjunatha 
Published: February 2023

AbstractVenom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulation in elapids is largely unexplored. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake,Pseudonaja textilis), in addition to comparative genomics, to identifycis- andtrans- acting regulation of venom production in an elapid in comparison to viperids (Crotalus viridisandC. tigris). Although there is conservation in high-level mechanistic pathways regulating venom production, there are histone methylation, transcription factor, and microRNA regulatory differences between these two snake families. Histone methyltransferases (KMT2A, KMT2C and KMT2D) and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFIcis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target different toxin transcripts. Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin evolution between these two snake families, demonstrating multiple toxin genes and regulatory mechanisms converged to underpin a highly venomous phenotype.
Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning
Authors: Perez Sofia Sedas , McQueen Caitlin , Pickering Joseph , Chinnaiya Kavitha , Saiz-Lopez Patricia , Ros Maria A. , Towers Matthew 
Published: February 2023

AbstractComplex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential requirement for AER-Fgf signalling duringin vivodevelopment makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenableex vivochick wing tissue explant system that faithfully replicatesin vivoparameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.
Floral volatiles evoke partially similar responses in both florivores and pollinators and are correlated with non-volatile reward chemicals
Authors: Sasidharan Rohit , Junker Robert R. , Eilers Elisabeth J. , Müller Caroline 
Published: February 2023

AbstractBackgroundPlants use floral displays to attract mutualists, but simultaneously need to prevent attacks by antagonists. Chemical displays detectable from a distance include attractive or repellent floral volatile organic compounds (FVOCs). Post-landing, visitors perceive contact chemicals including nutrients, but also deterrent or toxic constituents in pollen and nectar, protecting flowers from overexploitation. The composition of FVOCs and pollen chemistry is well known to vary among and within species. However, we lack knowledge about differences and similarities in the detectability of and behavioural responses towards these compounds for insect flower visitor groups of key importance, i.e., mutualistic pollinators versus antagonistic florivores, as well as the correlation between FVOCs and pollen chemodiversity.ScopeWe reviewed how FVOCs and non-volatile floral chemical displays, i.e., nutrients and toxins of pollen, vary in composition and how they affect the detection and behaviour of insect flower visitors. Moreover, we used a meta-analytic approach to evaluate the detection of and responses towards FVOCs by pollinators vs. florivores within the same plant genera. Furthermore, we tested whether the chemodiversity of FVOCs as well as nutrients and toxins stored in pollen are correlated and hence informative about each other.Key ResultsAccording to the available data, florivores are more likely to detect FVOCs than pollinators. Common FVOCs such as linalool and methyl salicylate were often reported as attractive to pollinators and repellent towards florivores. A higher number of FVOCs was found to be attractive to both mutualists and antagonists compared to shared repellent compounds. Furthermore, a negative correlation between FVOC richness and the number of pollen toxin classes was revealed, besides a trend towards a positive correlation between pollen protein amount and the number of pollen toxins.ConclusionsPlants face critical trade-offs when producing floral chemicals, as these partly mediate the same information, particularly attraction but also repellence or toxicity, to both mutualists and antagonists. Moreover, chemodiversity of different floral parts is partly correlated and thus highly relevant for investigations of flower-insect interactions. Further research is needed on more different wild and cultivated plant species and mutualistic and antagonistic interaction partners to test for generalisation of these patterns.
From Cell-Lines to Cancer Patients: Personalized Drug Synergy Prediction
Authors: Kuru Halil Ibrahim , Cicek A. Ercument , Tastan Oznur 
Published: February 2023

AbstractCombination drug therapies are effective treatments for cancer. However, the genetic heterogeneity of the patients and exponentially large space of drug pairings pose significant challenges for finding the right combination for a specific patient. Currentin silicoprediction methods can be instrumental in reducing the vast number of candidate drug combinations. However, existing powerful methods are trained with cancer cell line gene expression data, which limits their applicability in clinical settings. While synergy measurements on cell lines models are available at large scale, patient-derived samples are too few to train a complex model. On the other hand, patient-specific single-drug response data are relatively more available. In this work, we propose a deep learning framework,PersonalizedDeepSynergyPredictor (PDSP), that enables us to use the patient-specific single drug response data for customizing patient drug synergy predictions. PDSP is first trained to learn synergy scores of drug pairs and their single drug presonses for a given cell line using drug structures and large scale cell line gene expression data. Then, the model is fine-tuned for patients with their patient gene expression data and associated single drug response measured on the patientex vivosamples. In this study, we evaluate PDSP on data from three leukemia patients and observe that it improves the prediction accuracy by 27% compared to models trained on cancer cell line data. PDSP is built and available athttps://github.com/hikuru/PDSP
Delaying the GABA shift indirectly affects membrane properties in the developing hippocampus
Authors: Peerboom C. , De Kater S. , Jonker N. , Rieter M. , Wijne T. , Wierenga C.J. 
Published: February 2023

AbstractDuring the first two postnatal weeks intraneuronal chloride concentrations in rodents gradually decrease, causing a shift from depolarizing to hyperpolarizing γ-aminobutyric acid (GABA) responses. The postnatal GABA shift is delayed in rodent models for neurodevelopmental disorders and in human patients, but the impact of a delayed GABA shift on the developing brain remain obscure. Here we examine the direct and indirect consequences of a delayed postnatal GABA shift on network development in organotypic hippocampal cultures made from 6 to 7-day old mice by treating the cultures for one week with VU0463271, a specific inhibitor of the chloride exporter KCC2. We verified that VU treatment delayed the GABA shift and kept GABA signaling depolarizing until day in vitro (DIV) 9. We found that the structural and functional development of excitatory and inhibitory synapses at DIV9 was not affected after VU treatment. In line with previous studies, we observed that GABA signaling was already inhibitory in control and VU-treated postnatal slices. Surprisingly, fourteen days after the VU treatment had ended (DIV21), we observed an increased frequency of spontaneous inhibitory post-synaptic currents in CA1 pyramidal cells, while excitatory currents were not changed. Synapse numbers and release probability were unaffected. We found that dendrite-targeting interneurons in thestratum Radiatumhad an elevated resting membrane potential, while pyramidal cells were less excitable compared to control slices. Our results show that depolarizing GABA signaling does not promote synapse formation after P7, and suggest that postnatal intracellular chloride levels indirectly affect membrane properties in a cell-specific manner.Significance StatementDuring brain development the action of neurotransmitter GABA shifts from depolarizing to hyperpolarizing. This shift is a thought to play a critical role in synapse formation. A delayed shift is common in rodent models for neurodevelopmental disorders and in human patients, but its consequences for synaptic development remain obscure. Here, we delayed the GABA shift by one week in organotypic hippocampal cultures and carefully examined the consequences for circuit development. We find that delaying the shift has no direct effects on synaptic development, but instead leads to indirect, cell type-specific changes in membrane properties. Our data call for careful assessment of alterations in cellular excitability in neurodevelopmental disorders.
Tuning plant promoters using a simple split luciferase method for quantifying transcription factor binding affinity
Authors: Cai Y-M , Witham S , Patron NJ 
Published: February 2023

AbstractSequence features, including the binding affinity of binding motifs for their cognate transcription factors, are important contributors to promoter behavior. The ability to predictably recode affinity enables the development of synthetic promoters with varying levels of response to known cellular signals. Here we describe a luminescence-based microplate assay for comparing the interactions of transcription factors with short DNA probes. We then demonstrate how this data can be used to design synthetic plant promoters of varying strengths that respond to the same transcription.
Cementochronology using synchrotron radiation tomography to determine age at death and developmental rate in the holotype ofHomo luzonensis
Authors: van Heteren Anneke H. , King Andrew , Berenguer Felisa , Mijares Armand Salvador , Détroit Florent 
Published: February 2023

AbstractHomo luzonensis, a fossil hominin from the Philippines, is smaller than modern humans. At present, very little is known about the life history of this species. Cementochronology can answer life history questions, but usually involves destructive sampling. Here, we use synchrotron radiation to count the yearly cement lines of teeth belonging to a single individual. This approach allows us to determine that this individual was likely 31 years old at time of death and apparently had a developmental pattern comparable to chimpanzees. To our knowledge, this is the first time that cementochronology using synchrotron radiation tomography is used for life history and age-at-death estimation.