bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-existing intratumoral stem-like CD8+T-cells drive radiotherapy-induced tumor control
Authors: Köksal Hakan , Herbst Michael , Perreira Paulo , Nater Marc , Regli Nicola , Boudjeniba Cheïma , Borgoni Nese Erdem , Cecconi Virginia , Broek Maries van den 
Published: October 2024

SUMMARYCD8+T-cells are essential for spontaneous and therapy-induced restriction of tumor progression. Upon radiotherapy, these pre-existing CD8+T-cells expand rapidly after their initial decline and are essential and sufficient for early tumor control. Stem-like CD8+T-cells proliferate and differentiate into effector CD8+T-cells in response to radiotherapy and are thus key determinants of therapy efficacy. Our findings highlight the critical role of intratumoral stem-like CD8+T-cells in driving radiotherapy-induced anti-tumor immunity. Our study provides deeper insights into the dynamic behavior of CD8+T-cells and their critical involvement in tumor control following radiotherapy.
Investigating theDiuraphis noxia-Triticum aestivuminteraction using transcriptomics
Authors: Swiegers Hendrik W. , Foyer Christine H. , Botha Anna-Maria 
Published: October 2024

SummaryAphids often overcome host plant resistance by developing virulence. However, the underlying mechanisms and the precise modifications involved remain poorly understood. Additionally, the molecular response of resistant host plants during compatible (virulent aphid) and incompatible (avirulent aphid) interactions is another area requiring further investigation.Here,Diuraphis noxia(Russian wheat aphid) biotypes of varying virulence were transferred from susceptibleTriticum aestivumto a near-isogenic line containing theDn7resistance gene. Transcriptomes of theD. noxiabiotypes and the resistant host were sequenced before and after the host shift.Transcriptomic analysis indicated that theD. noxiabiotypes had unique responses which were involved in detoxification (e.g. L-xylulose reductase), membrane transport (e.g. Tert-1) and epigenetic regulation. In addition, many transposable elements were rapidly differentially regulated between biotypes and because of the host shift. In the host plant, all biotypes induced jasmonic acid signalling and terpenoid biosynthesis. However, the mono- and diterpenoid pathways were only upregulated following feeding by the biotypes avirulent toDn7and not SAMv2.Rapid differential expression of transposons suggests a mechanism of adaptation for clonally reproducing aphids. Furthermore, SAMv2 may possess mechanisms to modulate the defence response ofDn7-containingT. aestivum.
A deep learning approach to detect and visualise sexual dimorphism in monomorphic species
Authors: Silva Nicolas J. , Ferreira André C. , Silva Liliana R. , Perret Samuel , Tieo Sonia , Renoult Julien P. , Covas Rita , Doutrelant Claire 
Published: October 2024

AbstractSex recognition is facilitated by dimorphism in some traits. However, humans often fail to find the traits that allow to distinguish between sexes in other species. Deep learning has the potential to surpass humans in identifying cryptic differences between sexes, but, so far, has rarely been used to assess sexual dimorphism. In this study, we evaluated (i) the ability of a fine-tuned classification neural network, EfficientNet, to find differences between sexes in a species that appears monomorphic to humans, the sociable weaver (Philetairus socius). We then assessed (ii) the benefits of Grad-CAM visualisation techniques to understand which parts of the individuals are used by the network to differentiate the sexes. We trained 10-folds cross-validation models on more than 4,500 pictures of the head from more than 1,300 individuals. Our results show that the network can predict sex of sociable weavers with an accuracy of 76%, which is considerably higher than humans’ performance, and that the model was similarly good at predicting females and males. When interpreting the probability of being classified to one sex, our results further reveal an effect of the interaction of sex with age on the confidence score of the models which shows that younger males are less masculine than older ones, and older females more masculine than younger ones. Finally, using Grad-CAM we found that the model mostly uses the beak region to predict the sex of individuals. Overall, this work shows that artificial intelligence has the potential to be a non-invasive sexing tool, surpassing human capabilities and aiding in pinpointing potential cryptic dimorphic body parts that have yet to be identified. In birds, half of the world’s species appear sexually monomorphic to humans, and re-evaluation of species dimorphism with this type of methods could deepen our understanding of the effect of selection on animal traits.
Citrate synthase improves sepsis-induced lung injury by reconstructing the mitochondrial tricarboxylic acid cycle of macrophages
Authors: Sun Jiaojiao , Jin Sihao , Wang Zhiqiang 
Published: October 2024

AbstractBackgroundThe destruction of mitochondrial function during sepsis-induced acute lung injury (sepsis-ALI) can lead to tissue cell damage and organ dysfunction. Citrate synthase (CS) may maintain cellular energy metabolism by enhancing the mitochondrial tricarboxylic acid cycle (TCA cycle) in macrophages.Methods76 healthy donors and 89 sepsis patients were included. The levels of CS were determined using ELISA. We established a cecal ligation and puncture (CLP) model of sepsis to evaluate the effects of CS on lung injury by lung macrophages-specific CS knockdown or CS inhibitors. Isolated mouse lung macrophages were stimulated with LPS to observe the impact of CS overexpression and knockdown on TCA cycle.ResultsIn sepsis patients, CS was expressed at low levels and positively correlates with lung function parameters. In sepsis mice, knockdown CS or inhibiting its expression exacerbated lung injury and oxidative stress. In macrophages, inhibiting CS expression affected TCA cycle and worsened cell apoptosis, while overexpressing CS promoted TCA cycle, alleviating cell apoptosis, enhancing cellular energy production, and reducing oxidative stress levels. The supplementation of citric acid (a downstream metabolite of CS) helped alleviate mitochondrial damage and promotes the TCA cycle.ConclusionsThese results suggest that targeting CS may be a promising therapeutic approach for treating sepsis.
Effects of non-invasive brain stimulation on effective connectivity during working memory task in Neurofibromatosis Type 1 patients
Authors: Litwińczuk Marta Czime , Garg Shruti , Williams Stephen R. , Green Jonathan , Lea-Carnall Caroline , Trujillo-Barreto Nelson J 
Published: October 2024

AbstractThis study examined the effects of anodal transcranial direct current stimulation (atDCS) on effective connectivity during a working memory task. Eighteen adolescents with Neurofibromatosis Type 1 (NF1) completed a single□blind sham□controlled cross□over randomised atDCS trial. Dynamic causal modelling was used to estimate the effective connectivity between regions that showed working memory effects from the fMRI. Group-level inferences for between sessions (pre- and post-stimulation) and stimulation type (atDCS and sham) effects were carried out using the parametric empirical Bayes approach. A correlation analysis was performed to relate the estimated effective connectivity parameters of left dlPFC pre-atDCS and post-atDCS to the concentration of gamma-aminobutyric acid (GABA) measured via magnetic resonance spectroscopy (MRS-GABA). Next, correlation analysis was repeated using all working memory performance and all pre-atDCS and post-atDCS connectivity parameters. It was found that atDCS decreased average excitatory connectivity from left dorsolateral prefrontal cortex (dlPFC) to left superior frontal gyrus and increased average excitatory connectivity to left globus pallidus. Further, reduced average intrinsic (inhibitory) connectivity of left dlPFC was associated with lower MRS-GABA. However, none of the connectivity parameters of dlPFC showed any association with performance on a working memory task. These findings suggest that atDCS reorganised connectivity from frontal to fronto-striatal connectivity. As atDCS-related changes were not specific to the effect of working memory, they may have impacted general cognitive control processes. In addition, by reducing MRS-GABA, atDCS might make dlPFC more sensitive and responsive to external stimulation, such as performance of cognitive tasks.Highlights-atDCS was applied to left dlPFC in NF1 patients during working memory-After atDCS, no effect on modulatory connectivity-Evidence for increased N-back average connectivity from dlPFC to globus pallidus-Less dlPFC MRS-GABA was associated with less dlPFC inhibition
Lactate production from lactose-rich wastewater: A comparative study on reactor configurations to maximize conversion rates and efficiencies
Authors: Temovska Monika , Hegner Richard , Ortiz-Ardila Andrés E. , Usack Joseph G. , Angenent Largus T. 
Published: October 2024

ABSTRACTAbout 90% of global lactate production is derived from bacterial fermentation of sugarsviapure cultures of homofermentative bacteria in batch mode. Acid whey, which is a wastewater from the yogurt industry with lactose and galactose as the main sugars, can be used as an alternative substrate for the commercial production of lactate. Operating open cultures of microbial consortia (i.e., reactor microbiomes) reduces the costs of lactate production by circumventing sterilization, while continuous operation achieves higher productivity at shorter production times. Homofermentation can be achieved by maintaining acidic and thermophilic conditions, while product formation in continuous systems can be increased with biomass retention strategies. To find the best reactor configuration for lactate production from acid whey, we operated three different reactor configurations:(1)an upflow anaerobic sludge blanket (UASB) reactor;(2)an anaerobic filter reactor (AFR); and(3)an anaerobic continuously stirred tank reactor (CSTR) with a hollow-fiber membrane module. We operated at different hydraulic retention times (HRTs) to find the optimum parameters to maximize the lactose and galactose-into-lactate (LG-into-LA) conversion efficiency. We did not use an inoculum but enriched the endogenous D-lactate-producingLactobacillusspp. that later dominated the reactor microbiomes (> 90% relative abundance). Undissociated lactic acid concentrations of more than 60 mmol C L-1inhibited the microbiomes. We alleviated the inhibition effect by shortening the HRT to 0.6 days and using diluted acid-whey substrate (1.67-fold dilution) to achieve almost complete conversion of the acid-whey sugars to lactate. At the 0.6-day HRT commencement, the AFR and CSTR performed better than the UASB reactor due to their better cell retention abilities. During the period between Day 365-384, we experienced an error in the pH control of the CSTR system during which the pH value dropped to 4.3. After this pH-error period, the LG-into-LA conversion efficiency for the CSTR considerably improved and surpassed the AFR. We achieved the highest lactate conversion rate of 1256 ± 46.3 mmol C L-1d-1(1.57 ± 0.06 g L-1h-1) at a LG-into-LA conversion efficiency of 82.2 ± 3.4% (in mmol C), with a yield of 0.85 ± 0.02 mmol C mmol C-1(product per consumed substrate) for the CSTR.
Computational generation of long-range axonal morphologies
Authors: Berchet Adrien , Petkantchin Remy , Markram Henry , Kanari Lida 
Published: October 2024

AbstractLong-range axons are fundamental to brain connectivity and functional organization, enabling communication between different regions of the brain. Recent advances in experimental techniques have yielded a substantial number of whole-brain axonal reconstructions. While most previous computational generative models of neurons have predominantly focused on dendrites, generating realistic axonal morphologies is challenging due to their distinct targeting. In this study, we present a novel algorithm for axon synthesis that combines algebraic topology with the Steiner tree algorithm, an extension of the minimum spanning tree, to generate both the local and long-range compartments of axons. We demonstrate that our computationally generated axons closely replicate experimental data in terms of their morphological properties. This approach enables the generation of biologically accurate long-range axons that span large distances and connect multiple brain regions, advancing the digital reconstruction of the brain. Ultimately, our approach opens up new possibilities for large-scale in-silico simulations, advancing research into brain function and disorders.
Plasticity in cryoprotectant synthesis involves coordinated shunting away from pyruvate production
Authors: van der Burg Karin R. L. , Bozorgi Yasmin , Gyte Katie , Roe Amanda D. , Marshall Katie E. 
Published: October 2024

AbstractInsects living in temperate regions often accumulate a large amount of glycerol during winter to avoid freezing. This seasonal accrual of glycerol is generally produced from glycogen reserves through the pentose phosphate pathway. An alternative pathway to produce glycerol is through glycolysis, normally used for pyruvate production for eventual ATP synthesis. Aside from seasonal accumulation, some insects will also rapidly increase glycerol production as a short-term response to a sudden cold event, thereby increasing cold hardiness when necessary. In the eastern spruce budwormChoristoneura fumiferana, this plasticity in cold hardiness is locally adapted, where northern populations produce more glycerol upon cold shock. Here we investigate how glycerol is produced during the rapid plastic response to fluctuating cold conditions, and whether this pathway could be a target of local adaptation. After a period of repeated cold exposure, we found evidence of increased enzyme activity and increased mRNA abundance of several proteins associated with glycolysis, and a downregulation in expression of glucose-6-phosphate dehydrogenase, associated with pentose phosphate. Pyruvate production is prevented through downregulation of glyceraldehyde-3-phosphate dehydrogenase. We found higher overall enzyme activity and glycerol accumulation in a northern population from Alberta, although there was no evidence of an interaction effect between population and cold shock treatment. This is one the first studies to show a mechanistic basis of such plasticity in cold hardiness.
Genetic and functional diversity of allorecognition receptors in the urochordate,Botryllus schlosseri
Authors: Rodriguez-Valbuena Henry , Salcedo Jorge , De Their Olivier , Flot Jean Francois , Tiozzo Stefano , De Tomaso Anthony W 
Published: October 2024

AbstractAllorecognition inBotryllus schlosseriis controlled by a highly polymorphic locus (thefuhc), and functionally similar to missing-self recognition utilized by Natural Killer cells-compatibility is determined by sharing a self-allele, and integration of activating and inhibitory signals determines outcome. We had found these signals were generated by twofuhc-encoded receptors, calledfesteranduncle fester. Here we show thatfestergenes are members of an extended family consisting of >37 loci, and co-expressed with an even more diverse gene family-thefester co-receptors(FcoR). TheFcoRsare membrane proteins related tofester, but include conserved tyrosine motifs, including ITIMs and hemITAMs. Both genes are encoded in highly polymorphic haplotypes on multiple chromosomes, revealing an unparalleled level of diversity of innate receptors. Our results also suggest that ITAM/ITIM signal integration is a deeply conserved mechanism that has allowed convergent evolution of innate and adaptive cell-based recognition systems.
Identification and characterization of a wet adhesive protein extracted fromDreissena bugensis, the freshwater quagga mussel
Authors: Obille Angelico R. , Hasan Rida , Rees David J. , Ng Judith , Carneiro Karina M. M. , Sone Eli D. 
Published: October 2024

AbstractMechanisms of wet adhesion have been developed by several aquatic organisms over millions of years of evolutionary processes. Yet, the repertoire of synthetic biocompatible wet adhesive materials is still limited. In most marine bioadhesive proteins, 3,4-dihydroxyphenylalanine (DOPA) plays a significant role in strong interfacial interactions. The bioadhesive proteins in freshwater organisms are less well understood. The quagga mussel (Dreissena bugensis) is a notorious freshwater invasive species in the Great Lakes that attaches to a plethora of surfaces via a byssus. To determine the adhesive proteins in the quagga mussel byssus, we utilized quantitative proteomics to identify the proteins enriched at the byssus-substrate interface. Among the identified proteins was the Dbfp7 protein family. Dbfp7 is a small, polymorphic, and mostly disordered protein that lacks significant amounts of DOPA. Atomic force microscopy measurements of Dbfp7 confirm that this protein has similar adhesion energy to marine mussel adhesive proteins in aqueous conditions despite lacking DOPA. These results suggest that freshwater mussels may employ different mechanisms of adhesion compared to marine byssates. The inclusion of Dbfp7 to the library of known wet bioadhesive proteins – the first functionally characterized freshwater bioadhesive protein to our knowledge – will allow for a better understanding of the fundamental properties required to achieve biocompatible wet adhesion, a crucial step for the development of bio-inspired wet adhesive materials, such as improved medical adhesives.Significance StatementWhile many aquatic organisms evolved strategies to adhere to surfaces underwater, current synthetic biocompatible adhesives lack reliable adhesive strength in varying aqueous conditions. Investigating freshwater mussel adhesive proteins expands the current understanding of aquatic bioadhesion and offers potential advancements in wet adhesive technology. The discovery of a DOPA-deficient wet adhesive protein derived from the invasive quagga mussels presents a paradigm shift to the currently known mechanisms of byssal bioadhesion, thereby expanding the repertoire of wet adhesive strategies. Further, understanding the mechanism of adhesion employed by this biofouling species can help with the design of anti-fouling strategies to mitigate the impacts of these animals on the infrastructure and ecosystems in the Great Lakes and connected freshwater systems in North America.
Prolonged Hyperactivity Elicits Massive and Persistent Chloride Ion Redistribution in Subsets of Cultured Hippocampal Dentate Granule Cells
Authors: Takano Hajime , Hsu Fu-Chun , Coulter Douglas A. 
Published: October 2024

ABSTRACTChloride ions play a critical role in neuronal inhibition through the activity of chloride-permeable GABAAreceptor channels. Ion transporters, chloride channels, and immobile ion species tightly regulate intracellular chloride concentrations. Several studies related to epilepsy suggest that chloride extrusion function may decrease in an activity-dependent manner. Consequently, it is crucial to investigate whether intense neuronal activity, as observed during status epilepticus, could lead to sustained increases in intracellular chloride levels in neurons, which in turn could contribute to epilepsy-associated hyperexcitability. This study utilized the chloride sensitive indicator (6-Methoxyquinolinio) acetic acid ethyl ester bromide (MQAE) combined with fluorescence lifetime imaging (FLIM) to examine whether application of the convulsant, pilocarpine, a muscarinic acetylcholine receptor agonist, could induce synchronous epileptiform activity and elevate intracellular chloride concentrations in hippocampal slice cultures. Using a Gaussian mixture model, we identified a multimodal distribution of intracellular chloride levels among neurons, with a significant subset of these cells exhibiting massive and prolonged (days) chloride accumulation. The combination of multicellular imaging and statistical analysis served as a powerful tool for studying the emergence of multiple, distinct populations of neurons in pathological conditions, in contrast to homogeneous populations evident under control conditions.HighlightsMaintaining low [Cl−]inis important for inhibitory function, however, hyperactivity, such as that seen in epilepsy, may lead to elevated [Cl−]in.Pilocarpine induces hyperactivity in dentate granule cells (DGCs) in hippocampal organotypic slice cultures.Multicellular imaging using a chloride sensing dye with a fluorescence lifetime imaging approach revealed that [Cl−]inis elevated in a subpopulation of DGCs.Gaussian mixture model analysis is a powerful tool for studying the emergence of cellular heterogeneity in a pathological condition.Graphic Abstract
An AI-Driven Model of Consciousness, Its Disorders, and Their Treatment
Authors: Toker Daniel , Thum Jasmine A. , Guang Jing , Miyamoto Hiroyuki , Yamakawa Kazuhiro , Vespa Paul M. , Schnakers Caroline , Bari Ausaf A. , Hudson Andrew , Pouratian Nader , Monti Martin M. 
Published: October 2024

AbstractUnderstanding the neural signatures of consciousness and the mechanisms underlying its disorders, such as coma and unresponsive wakefulness syndrome, remains a critical challenge in neuroscience. In this study, we present a novel computational approach for the in silico discovery of neural correlates of consciousness, the mechanisms driving its disorders, and potential treatment strategies. Inspired by generative adversarial networks, which have driven recent advancements in generative artificial intelligence (AI), we trained deep neural networks to detect consciousness across multiple brain areas and species, including humans. These networks were then integrated with a genetic algorithm to optimize a brain-wide mean-field model of neural electrodynamics. The result is a realistic simulation of conscious brain states and disorders of consciousness (DOC), which not only recapitulates known mechanisms of unconsciousness but also predicts novel causes expected to lead to these conditions. Beyond simulating DOC, our model provides a platform for exploring therapeutic interventions, specifically deep brain stimulation (DBS), which has shown promise in improving levels of awareness in DOC in over five decades of study. We systematically applied simulated DBS to various brain regions at a wide range of frequencies to identify an optimal paradigm for reigniting consciousness in this cohort. Our findings suggest that in addition to previously studied thalamic and pallidal stimulation, high-frequency stimulation of the subthalamic nucleus, a relatively underexplored target in DOC, may hold significant promise for restoring consciousness in this set of disorders.