bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inkube: An all-in-one solution for neuron culturing, electrophysiology, and fluidic exchange
Authors: Maurer Benedikt , Fassbind Selina , Ruff Tobias , Duru Jens , Spacone Giusy , Rodde Theo , Vörös János , Ihle Stephan J. 
Published: December 2024

Culturing neuronal networksin vitrois a tedious and time-consuming endeavor. In addition, how the composition of the culture medium and environmental variables such as temperature, osmolarity, and pH affect the spiking behavior of neuronal cultures is difficult to study using electrophysiology. In this work, we present “inkube”, an incubation system that has been combined with an electrophysiology setup and a fully automatic perfusion system. This setup allows for the precise measurement and control of the temperature of up to 4 microelectrode arrays (MEAs) in parallel. In addition, neuronal activity can be electrically induced and recorded from the MEAs. inkube can continuously monitor the medium level to automatically readjust osmolarity. Using inkube’s unique capability to precisely control the environmental variables of a neural culture, we found that medium evaporation influences the spiking response. Moreover, decreasing medium temperature by only 1.5°C significantly affected spike latency, a measure commonly used to show plasticity inin vitroexperiments. We finally provide a proof-of-concept experiment for drug screening applications, where inkube automatically and precisely varies the concentration of magnesium ions in the medium. Given its high level of autonomy, the system can record, stimulate, and control the medium continuously without user intervention. Both the hardware and the software of inkube are completely open-source.HighlightsLow-cost, open-hardware/open-software electrophysiology setupFull incubation solution: Temperature, CO2, and humidity controlPerfusion system for automatic fluidic exchange and drug testing with volume feedback
Orchids, hawkmoths and Darwin revisited: How adaptation to pollination by hawk-moths spurred the speciation of Old and New World angraecoids
Authors: Farminhão João , Collobert Géromine , Perez-Lamarque Benoît , Verlynde Simon , Ramandimbisoa Brigitte , Kaymak Esra , Azandi Laura , Droissart Vincent , Simo-Droissart Murielle , Johnson Steve , Martos Florent , Stévart Tariq 
Published: December 2024

ABSTRACTSpecialised pollination has often been proposed as a major driver of the unrivalled diversification of angiosperms. With its unparalleled variation in flower depth, ranging from spurless to 40 cm spurred flowers pollinated by hawkmoths, angraecoid orchids (Angraecinae) provide unique opportunities to reveal the impact of floral specialisation on diversification rates in the Afrotropics and Neotropics. We compiled floral characters for 327 angraecoid species, and assigned these species to newly formalised floral syndrome categories calibrated against pollination case studies. We then estimated ancestral character states and state-dependent speciation rates using the latest time-calibrated phylogeny of angraecoids. We found that white flowers consistent with micro-sphingophily (2 cm≥ spurs <8.7 cm), macro-sphingophily (8.7 cm≥ spurs <18.6 cm) and mega-sphingophily (spurs ≥18.6 cm) evolved repeatedly in angraecoids, and are ancestral in some non-sphingophilous clades. Reversals to non-sphingophily and pigmented flowers suggest higher evolutionary lability of these traits than what is traditionally thought. Increasing floral specialisation with long spurs does not seem to enhance angraecoid orchids’ speciation rates, since micro-sphingophily appears to be associated with the highest speciation rates. An abundance of short-proboscid hawkmoths in Madagascar, as an ecological opportunity, may have accelerated the speciation of micro-sphingophilous taxa.
Virtual clinical trial reveals significant clinical potential of targeting tumour-associated macrophages and microglia to treat glioblastoma
Authors: Mongeon Blanche , Craig Morgan 
Published: December 2024

AbstractGlioblastoma is the most aggressive primary brain tumour, with a median survival of just fifteen months with treatment. Standard-of-care (SOC) for glioblastoma consists of resection followed by radio- and chemotherapy. Clinical trials involving PD-1 inhibition with nivolumab in combination with SOC failed to increase overall survival. A quantitative understanding of the interactions between the tumour and its immune environment driving treatment outcomes is currently lacking. As such, we developed a mathematical model of tumour growth that considers cytotoxic CD8+ T cells, pro- and antitumoral tumour-associated macrophages and microglia (TAMs), SOC, and nivolumab. Our results show that PD-1 inhibition fails due to a lack of CD8+ T cell recruitment during treatment explained by TAM-driven immunosuppressive mechanisms. Using our model, we studied five TAM-targeting strategies currently under investigation for solid tumours. Our model predicts that while reducing TAM numbers does not improve prognosis, altering their functions to counter their protumoral properties has the potential to considerably reduce post-treatment tumour burden. In particular, restoring antitumoral TAM phagocytic activity through anti-CD47 treatment in combination with SOC was predicted to nearly eradicate the tumour. By studying time-varying efficacy with the same half-life as the anti-CD47 antibody Hu5F9-G4, our model predicts that repeated dosing of anti-CD47 provides sustained control of tumour growth. Thus, we propose that targeting TAMs by enhancing their antitumoral properties is a highly promising avenue to treat glioblastoma and warrants future clinical development. Together, our results provide proof-of-concept that mechanistic mathematical modelling can uncover the mechanisms driving treatment outcomes and explore the potential of novel treatment strategies for hard-to-treat tumours like glioblastoma.
Staying on track: collagen fibers orientation strongly affects thrombi formation at high shear
Authors: Melnikova E.A. , Mangin P.H. , Panteleev M.A. , Nechipurenko D.Y. 
Published: December 2024

AbstractObjectiveSubendothelial matrix exhibits a distinctive organization, with collagen fibers beneath the endothelium oriented primarily parallel to the flow and comprising mainly types III and I collagen in arteries and arterioles. However, the significance of such organization in initiating rapid thrombus formation remains unclear.Approach and ResultsTo investigate the role of collagen fibers orientation in triggering thrombus formation we utilized thein vitromicrofluidic model of thrombosis. Human whole blood was perfused through a system with collagen fibers oriented either parallel or perpendicular to the flow, and the primary stages of platelet adhesion and thrombi growth were analyzed using a high-speed fluorescence microscopy.At the shear rates of 200 and 1000 s-1no significant difference in thrombogenicity was observed between the collagen fibers orientations. However, at a high shear rate of 2000 s-1, thrombi on the parallel fibers were higher and covered a much larger area than those on the perpendicular ones. High-speed microscopy revealed that platelets were able to achieve stable adhesion only after translocating for over several seconds under all studied conditions. Analysis of single platelets dynamics revealed that platelets interacted longer and translocated farther during their interaction with parallel fibers at high shear, suggesting that flow-aligned fibers facilitate stable adhesion by enabling platelets to translocate along them and stay in contact with collagen. Importantly, only a small fraction of collagen fibers belonging to type III collagen admixture - a common component of a standard type I collagen preparation - accumulated plasma vWF and supported platelet adhesion at high shear rate.ConclusionType III, but not type I collagen fibers oriented parallel to the flow facilitate stable platelet adhesion at high shear rates. Thus, axial orientation of subendothelial collagen fibers observedin vivomay have physiological relevance for triggering rapid thrombus formation at high shear rates.Graphical abstract
Ionic Liquid-Induced Modulation of Ubiquitin Stability: The Dominant Role of Hydrophobic Interactions
Authors: Shrivastava Aditya , Kamma Harika , Das Ranabir , Ainavarapu Sri Rama Koti 
Published: December 2024

AbstractDespite the widespread use of imidazolium-based ionic liquids (ILs) in biotechnology, pharmaceuticals, and green chemistry, their detailed interactions with proteins, particularly affecting structural stability, remain poorly understood. This study examines the effects of ILs on ubiquitin, a thermodynamically robust protein with a β-grasp structure. We found that IL-induced destabilisation follows a consistent order with previous findings: [BF4]-> [MeSO4]-> [Cl]-for anions and [BMIM]+> [BMPyr]+> [EMIM]+for cations. Through pH and ionic strength-dependent studies, we observed that hydrophobic interactions predominantly influence the stability of positively charged ubiquitin, with electrostatic interactions playing a secondary role. NMR studies identified residues impacted by [BMIM][BF4]; however, mutagenesis of these residues showed minimal changes in destabilisation, suggesting a global effect. This led us to conduct a broader empirical analysis, incorporating solvent-accessible surface area evaluations, which confirmed that hydrophobic residues are the primary drivers of stability alterations in ubiquitin, with charged residues playing a minimal role. Additionally, single-molecule force spectroscopy results indicate that imidazolium ILs decrease the unfolding barrier without altering transition state structures, offering insights into protein folding dynamics. ILs appear to modulate the stability landscape of proteins by energetically and kinetically favouring the unfolded state over the folded state. These insights offer potential strategies for the selective tuning of protein stability, which could be exploited to modulate protein-protein or protein-substrate interactions in various applications of ILs.
OrthoHMM: Improved Inference of Ortholog Groups using Hidden Markov Models
Authors: Steenwyk Jacob L , Buida Thomas J. , Rokas Antonis , King Nicole 
Published: December 2024

AbstractAccurate orthology inference is essential for comparative genomics and phylogenomics. However, orthology inference is challenged by sequence divergence, which is pronounced among anciently diverged organisms. We present OrthoHMM, an algorithm that infers orthologous gene groups using Hidden Markov Models parameterized from substitution matrices, which enables better detection of remote homologs. Benchmarking indicates OrthoHMM outperforms currently available methods; for example, using a curated set of Bilaterian orthogroups, OrthoHMM showed a 10.3 – 138.9% improvement in precision. Rank-based benchmarking using Bilaterian orthogroups and a novel dataset of orthogroups from organisms in three major eukaryotic kingdoms revealed OrthoHMM had the best overall performance (6.7 – 97.8% overall improvement). These findings suggest that Hidden Markov Models improve orthogroup inference.
Vitrification and rapid rewarming of precision-cut liver slices for pharmacological and biomedical research
Authors: Ramesh Srivasupradha , Rao Joseph Sushil , Namsrai Bat-Erdene , Fisher Benjamin , Tobolt Diane K. , Megaly Michael , Etheridge Michael L. , Pruett Timothy L. , Seelig Davis , Murugan Paari , Aldaraiseh Bashar , Finger Erik B. , Bischof John C. 
Published: December 2024

AbstractBackground and AimsHigh-throughput in vitro pharmacological toxicity testing is essential for drug discovery. Precision-cut liver slices (PCLS) provide a robust system for screening that is more representative of the complex 3D structure of the whole liver than isolated hepatocytes. However, PCLS are not available as off-the-shelf products, significantly limiting their translational potential. Cryopreservation could solve this bottleneck by effectively preserving PCLS indefinitely until their time of use. Conventional cryopreservation (slow cooling in DMSO-forming ice) results in poor PCLS viability and function and, therefore, has proven unsuitable. Here, we explore an “ice-free” cryopreservation approach called vitrification and focus on culturing and assessing PCLS for 3 days post-vitrification and rewarming, given that most acute drug toxicity tests are conducted over 24h.MethodsRat liver slices were diffusively loaded with a cryoprotective agent (CPA) cocktail consisting of EG and Sucrose. The CPA-loaded PCLS were placed on a polymer cryomesh, vitrified in liquid nitrogen (LN2), and rapidly rewarmed in CPA. The vitrified and rewarmed PCLS were subsequently cultured in a controlled volume of serum-free, chemically defined media for 3 days.ResultsThe cryopreserved PCLS maintained high viability, morphology, function, enzymatic activity, and drug toxicity response. Results show that the vitrified PCLS perform comparably to untreated controls and significantly outperform conventionally cryopreserved PCLS in all assessments (p< 0.05).ConclusionsRapid vitrification and rewarming of PCLS using cryomesh enabled successful preservation and culture. This approach maintained high viability, function, enzymatic activity, and drug response for 3 days in culture, similar to controls.Impact and ImplicationsThe implications of using vitrification to store PCLS are extensive. This technology provides an exciting opportunity for the development of an “off-the-shelf” cold supply chain of human PCLS from organs declined for transplant, which are sliced, cryopreserved, and stored in a repository and available for on-demand shipping for industrial and academic biomedical research. This would also allow PCLS to become a scalable, reproducible, wide-ranging, and population-representative source of tissue that can accurately mimic in-vivo conditions of the human liver. These transformative technologies could revolutionize our practice in studying not just the metabolism of drugs but also increase our capacity to study the zonal progression of many liver diseases and conduct other exciting biomedical research.
Biophysical modeling of thalamic reticular nucleus subpopulations and their differential contribution to network dynamics
Authors: Litvak Polina , Hartley Nolan D. , Kast Ryan , Feng Guoping , Fu Zhanyan , Arnaudon Alexis , Hill Sean L. 
Published: December 2024

AbstractThe burst firing mode of thalamic reticular neurons plays a pivotal role in the generation and maintenance of sleep rhythms and is implicated in sleep-related deficits characteristic of neurodevelopmental disorders. Although several models of reticular neurons have been developed to date, we currently lack a biophysically detailed model able to accurately reproduce the heterogeneity of burst firing observed experimentally. Using electrophysiology recordings of patch-clamped fluorescently tagged Spp1+ and Ecel1+ reticular neurons, we leverage a previously established statistical framework to introduce differentiation of cell types in model thalamic reticular neurons. We developed a population of biophysically detailed models of thalamic reticular neurons that capture the diversity of their firing properties, particularly their ability to generate rebound bursts. These models incorporate key ion channels, such as T-type Ca2+and small conductance potassium channels (SK), and enable systematic investigations into the impact of these channels on single-cell dynamics. By integrating these models into a thalamic microcircuit, we demonstrate that T-type Ca2+and SK channel conductances have opposing effects on spindle oscillations. We identify a simple relationship between these conductances and the peak firing frequency of spindles, maintained across circuits with mixed reticular neuron populations, providing a framework for understanding how ion channel expression influences thalamic network dynamics. Collectively, these models establish a foundation for relating intrinsic cellular properties of reticular cell populations to network-level activity in both healthy and pathological conditions.
Validating Atlantic salmon (Salmo Salar) scale reading by genetic parent assignment and PIT-tagging
Authors: Utne Kjell Rong , Brieuc Marine Servane Ono , Fjeldheim Per Tommy , Urdal Kurt , Østborg Gunnel Marie , Glover Kevin A. , Harvey Alison , Skaala Øystein 
Published: December 2024

AbstractUnderstanding changes in abundance and survival in Atlantic salmon populations requires knowledge of growth rates and age. Salmon are typically aged through scale reading, but such estimates are rarely validated against age-verified fish from the wild. Here, we present a unique dataset of scales from 254 PIT-tagged Atlantic salmon with known sea-age. In addition, the freshwater age is known for 81 of these fish, through genetic parent-offspring identification. This dataset was used to estimate precision and bias in age readings and back-calculated length, as estimated by three independent experienced salmon scale readers. Overall, readers had an accuracy of 97.1% for sea-age and 71.7% for freshwater-age. For sea-age, scale reading was less accurate for salmon that had spent 2 or more years at sea than for salmon that had spent 1 year at sea. Freshwater age did however not affect scale reading accuracy. None of the scale readers erroneously misclassified freshwater-or sea-age with more than one year, and there was no significant pattern of misclassified ages to be under-or overestimate by the scale readers. Back-calculated smolt length was significantly different to length when measured as a smolt prior to seaward migration: it was shorter than the measured body-length for small smolts and longer for large smolts. This unique dataset, including the age-validated images of all scales, is now made openly available providing an important resource for training and testing salmon scale readers globally.
Simulating the diffusion of PPR-like disease to improve surveillance
Authors: Mesdour Asma , Ijoma Sandra , Bolajoko Muhammad-Bashir , Ciss Mamadou , Cardinale Eric , Eubank Stephen , Andraud Mathieu , Apolloni Andrea 
Published: December 2024

ABSTRACTAnimal mobility is a founding element of pastoral culture and fundamental to the economy in West Africa. Herds’ movement, involving mainly cattle, sheep, and goats, is vital for adapting to climate fluctuations, optimizing natural resources, and managing risks in livestock production, as well as livestock trade and exchanges. However, these movements contribute to the spread of transboundary animal diseases such as Peste des petits ruminants (PPR). Nigeria experienced its first PPR outbreak in the 1960s-1970s, and outbreaks have regularly occurred since then. Yet, no adequate surveillance system has been put in place, and the absence of proper animal movement tracking remains a critical shortcoming in addressing this ongoing threat. Because of this, we rely onad-hocactivities, like mobility surveys, to collect this information. However, these data could be partial and limited in time and space, hindering the capacity to identify suitable areas for monitoring disease circulation (sentinel nodes). Market survey data from three northern states are collected once to reconstruct the small ruminant mobility network. A group of areas with a high potential to infect each other were identified (Contagion Cluster). A stochastic Susceptible-Infected-Recovered (SIR) was used to simulate the spread of a PPR-like disease through movements. Sentinel nodes and their key characteristics were identified using Random Forest classification. The network (missing movement) was predicted with a hierarchical random graph (HRG), and uncertainty analysis assessed the effects of missing movements on the epidemic extent and identity and characteristics of sentinel nodes. The number of sentinel nodes varied with the epidemic’s severity, but their characteristics remained consistent. The uncertainty analysis results showed that adding 1% of the most probable missing links did not affect the final size of the epidemic. However, a significant difference appears when adding more than 3% of the missing links, causing a gradual fluctuation in the epidemic’s final size. The final size of the epidemic stabilized when adding more than 50% of the most probable links. The challenge posed by incomplete animal movement data underscores the need for further research and data collection efforts. However, predicting missing links presents a promising method for enhancing the reliability of epidemic prediction and sentinel node identification. This potential to improve disease surveillance and control strategies is a significant implication of our study.
Rats pursue food and leisure following the same rational principles
Authors: Logue Raegan S. , Garcia Ana K. , Bejarano Brissa A. , Kendall Riley K. , Wikenheiser Andrew M. 
Published: December 2024

AbstractAnimals in the wild must balance multiple, potentially mutually-exclusive goals simultaneously in order to survive. Yet laboratory tests of decision making often investigate how animals optimize their behavior to achieve a single, well-defined goal, which is often a nutritive reward. Thus, how animals solve multi-objective optimization problems is not well understood. Here, we devised an ethologically-inspired decision making task to examine how rats balance the pursuit of food and non-food reinforcement. Rats performed a free-choice patch-foraging task, in which they could earn food in one location (food patch) or interact with a rodent play structure in a different location (toy patch). The cost of switching between patches was manipulated by requiring rats to endure a long or short “travel time” penalty during which they were not able to access either patch. Rats devoted a considerable amount of their limited foraging time to patches of both types, showing a small but significant preference for food patches. In accordance with theoretical models of foraging, when the cost of switching patches was high rats chose longer stay durations in both types of patches, suggesting that similar rational principles guided their pursuit of food and non-food rewards. Examining the within-session dynamics of time allocation revealed that rats showed an early preference for spending time in toy patches that reversed over the course of the session. These results validate a naturalistic approach to testing decision making in rats over a range of food and non-food goods.
Enhancing Two-Dimensional Control via Single-Channel Haptic Feedback: A Multi-dimensional Encoding Strategy
Authors: Benigni T R , Pena A , Kuntaegowdanahalli S , Abbas J J , Jung R 
Published: December 2024

AbstractRecently a multidimensional encoding approach to direct stimulation of a single site in the median nerve showed that an intensity and flutter frequency could be perceived and graded. It is unclear whether these two dimensions are able to convey useful information to participants performing control tasks or whether they improve on typical intensity only modulation approach. Eleven participants performed experiments to assess the efficacy of multidimensional stimulation. In a set of discrete matching tasks, participants were able to correctly identify all thirteen discrete stimulation points better than chance. In a modified center-out task, and three separate extremes-in tasks, all seventeen changes in the stimulation parameters could be detected better than chance. Performance of the discrete task using a multidimensional approach showed increased information transfer compared to the individual modulation of intensity or flutter frequency. The results suggest that multidimensional encoding is a promising approach for increasing information throughput in sensory feedback systems. By investigating a multimodal encoding approach, this study offers valuable insights into haptic feedback through peripheral nerve stimulation. This haptic feedback might offer pronounced benefits for virtual reality applications and individuals with upper limb amputations opening avenues for an enhanced sensory feedback experience.