bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global DNA Hypomethylation as a Biomarker of Accelerated Epigenetic Ageing in Primates
Authors: Girling Michael T.S. , Sanchez Nofre M , Paredes Ursula M. 
Published: March 2024

ABSTRACTIntroductionEpigenetic clocks based on DNA methylation patterns provide a powerful tool for measuring biological ageing, but requiring genome-wide methylation data and high costs limits their broad application across species and populations.MethodsWe investigated whether simply quantifying global DNA methylation levels could serve as an inexpensive proxy for epigenetic ageing, using a captive colony of owl monkeys (Aotus nancymaae) using a colorimetric ELISA assay to measure proportional content of levels of blood and brain 5-methylcytosine (5-mC) across the genome, comparing owl monkeys with known exposures to ageing accelerators and controls.Resultswe found that global 5-mC declined significantly with chronological age in blood, and in the brain of parents. Notably, this age-related blood hypomethylation in individuals experiencing early life maternal rejection was accelerated. Parenting experience also accelerated DNA methylation loss with age, but this effect was specific to the brain and not seen in blood. Infection history did not impact blood 5-mC trajectories. Although multiple regression models did not replicate all findings, likely due to sample size constraints, our results demonstrate that global DNA hypomethylation tracks biological ageing in blood.DiscussionThis simple metric successfully detected accelerated epigenetic ageing induced by early adversity, as well as distinct patterns relating to reproductive investment in the brain - phenotypes typically identified by sophisticated epigenetic clocks. Quantifying global methylation thus provides a cost-effective alternative approach to assessing susceptibility to environmentally-driven accelerated ageing across primate species and populations where DNA methylation arrays or sequencing are impractical.
Multiple and subject-specific roles of uncertainty in reward-guided decision-making
Authors: Paunov Alexander , L’Hôtellier Maëva , Guo Dalin , He Zoe , Yu Angela , Meyniel Florent 
Published: March 2024

AbstractDecision-making in noisy, changing, and partially observable environments entails a basic tradeoff between immediate reward and longer-term information gain, known as the exploration-exploitation dilemma. Computationally, an effective way to balance this tradeoff is by leveraging uncertainty to guide exploration. Yet, in humans, empirical findings are mixed, from suggesting uncertainty-seeking to indifference and avoidance. In a novel bandit task that better captures uncertainty-driven behavior, we find multiple roles for uncertainty in human choices. First, stable and psychologically meaningful individual differences in uncertainty preferences actually range from seeking to avoidance, which can manifest as null group-level effects. Second, uncertainty modulates the use of basic decision heuristics that imperfectly exploit immediate rewards: a repetition bias and win-stay-lose-shift heuristic. These heuristics interact with uncertainty, favoring heuristic choices under higher uncertainty. These results, highlighting the rich and varied structure of reward-based choice, are a step to understanding its functional basis and dysfunction in psychopathology.
Hippocampal Signal Complexity and Rate-of-Change Predict Navigational Performance: Evidence from a Two-Week VR Training Program
Authors: Ozubko Jason D. , Campbell Madelyn , Verhayden Abigail , Demetri Brooke , Brady Molly , Sivashankar Yadurshana , Brunec Iva 
Published: March 2024

AbstractThe hippocampus is believed to be an important region for spatial navigation, helping to represent the environment and plan routes. Evidence from rodents has suggested that the hippocampus processes information in a graded manner along its long-axis, with anterior regions encoding coarse information and posterior regions encoding fine-grained information. Brunec et al. (2018) demonstrated similar patterns in humans in a navigation paradigm, showing that the anterior-posterior gradient in representational granularity and the rate of signal change exist in the human hippocampus. However, the stability of these signals and their relationship to navigational performance remain unclear. In this study, we conducted a two-week training program where participants learned to navigate through a novel city environment. We investigated inter-voxel similarity (IVS) and temporal auto-correlation hippocampal signals, measures of representational granularity and signal change, respectively. Specifically, we investigated how these signals were influenced by navigational ability (i.e., stronger vs. weaker spatial learners), training session, and navigational dynamics. Our results revealed that stronger learners exhibited a clear anterior-posterior distinction in IVS in the right hippocampus, while weaker learners showed less pronounced distinctions. Additionally, lower general IVS levels in the hippocampus were linked to better early learning. Successful navigation was characterized by faster signal change, particularly in the anterior hippocampus, whereas failed navigation lacked the anterior-posterior distinction in signal change. These findings suggest that signal complexity and signal change in the hippocampus are important factors for successful navigation, with IVS representing information organization and auto-correlation reflecting moment-to-moment updating. These findings support the idea that efficient organization of scales of representation in an environment may be necessary for efficient navigation itself. Understanding the dynamics of these neural signals provides insights into the mechanisms underlying navigational learning in humans.
Characterisation of cuticle mechanical properties: analysing stiffness in layered living systems to understand surface buckling patterns
Authors: Airoldi Chiara A. , Chen Chao , Herrera-Ubaldo Humberto , Fu Hongbo , Lugo Carlos A. , Crosby Alfred J. , Glover Beverley J. 
Published: March 2024

ABSTRACTDevelopment of a living organism is a highly regulated process during which biological materials undergo constant change.De novomaterial synthesis and changes in mechanical properties of materials are key for organ development; however, few studies have attempted to produce quantitative measurements of the mechanical properties of biological materials during growth. Such quantitative analysis is particularly challenging where the material is layered, as is the case for the plant cuticle on top of the plant epidermal cell wall. Here, we focus onHibiscus trionumflower petals, where buckling of the cuticle forms ridges, producing an iridescent effect. This ridge formation is hypothesised to be due to mechanical instability, which directly depends upon the mechanical properties of the individual layers within the epidermal cells. We present measurements of the mechanical properties of the surface layers of petal epidermal cells through atomic force microscopy (AFM) and the uniaxial tensile tester for ultrathin films (TUTTUT), across growth stages. We found that the wavelength of the surface ridges was set at the ridge formation stage, and this wavelength was preserved during further petal development, most likely because of the plasticity of the material. Our findings suggest that temporal changes in biological material properties are key to understanding the development of biological surface patterns.
Nonuniform scaling of synaptic inhibition in the dorsolateral geniculate nucleus in a mouse model of glaucoma
Authors: Van Hook Matthew J. , McCool Shaylah 
Published: March 2024

AbstractElevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC signaling to visual centers of the brain such as the dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information to the cortex for conscious vision. In response to altered levels of activity or synaptic input, neurons can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them to scale their synaptic responses to stabilize spike output. While prior work has indicated unaltered glutamate receptor properties in the glaucomatous dLGN, it is unknown whether glaucoma impacts dLGN inhibition. Here, using DBA/2J mice, which develop elevated IOP beginning at 6-7 months of age, we tested whether the strength of inhibitory synapses on dLGN thalamocortical relay neurons is altered in response to the disease state. We found an enhancement of feed-forward disynaptic inhibition arising from local interneurons along with increased amplitude of quantal inhibitory synaptic currents. A combination of immunofluorescence staining for the GABAA-α1 receptor subunit, peak-scaled nonstationary fluctuation analysis, and measures of homeostatic synaptic scaling indicated this was the result of an approximately 1.4-fold increase in GABA receptor number at post-synaptic inhibitory synapses, although several pieces of evidence strongly indicate a non-uniform scaling across inhibitory synapses within individual relay neurons. Together, these results indicate an increase in inhibitory synaptic strength in the glaucomatous dLGN, potentially pointing toward homeostatic compensation for disruptions in network and neuronal function triggered by increased IOP.Significance Statement:Elevated eye pressure in glaucoma leads to loss of retinal outputs to the dorsolateral geniculate nucleus (dLGN), which is critical for relaying information to the cortex for conscious vision. Alterations in neuronal activity, as could arise from excitatory synapse loss, can trigger homeostatic adaptations to synaptic function that attempt to maintain activity within a meaningful dynamic range, although whether this occurs uniformly at all synapses within a given neuron or is a non-uniform process is debated. Here, using a mouse model of glaucoma, we show that dLGN inhibitory synapses undergo non-uniform upregulation due to addition of post-synaptic GABA receptors. This is likely to be a neuronal adaptation to glaucomatous pathology in an important sub-cortical visual center.
Oncogenic Phase Transitions: How Mutant p53 Drives Amyloid Formation in p63 and p73 Liquid Droplets
Authors: Petronilho Elaine C. , de Andrade Guilherme C. , de Sousa Gileno dos S. , Almeida Fernando P. , Mota Michelle F. , Marques Mayra A. , Vieira Tuane C. R. G. , de Oliveira Guilherme A. P. , Silva Jerson L. 
Published: March 2024

AbstractPhase separation (PS) of p53 is critical in its path to amyloid aggregation, a process linked to cancer. P63 and p73 exhibit dual roles as tumor suppressors and oncogenes and are often heightened in tumors. Their coaggregation has been proposed in cancer, yet their PS contribution remains unknown. This study investigates the phase behaviors of p53, p63, and p73. P63 and p73 undergo liquid-liquid phase separation (LLPS). Unlike p53, p63 and p73 do not form amyloids under increased temperatures, underscoring an aspect of the processes involved in cancer. Unlike p63 and p73, wild-type and the M237I mutant p53 initially form droplets at 4°C, but at temperatures up to 37°C, they begin to aggregate and bind to Congo red, showing amyloidogenesis. Intriguingly, mutant p53 promotes amyloid-like states in p63 and p73 and hijacks p73 into membrane less organelles. Wild-type p53 has a moderate effect on p63 and p73’s amyloid aggregation. Additionally, heparin prevents the prion-like aggregation of p63 and p73 induced by p53. Our results shed light on how mutant and wild-type p53 may trigger amyloid aggregation of p63 and p73, revealing the capacity of p53 amyloid droplets within cancer. These insights expand the possibilities for developing cancer therapies targeting the prion-like conversion of p63 and p73 influenced by mutated p53.RelevanceThe prion-like action of mutant p53 on p63 and p73 droplets would be the basis for an oncogenic gain of function of the p53 mutation.
Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses
Authors: Dey Abhishek , Yan Shuting , Schlick Tamar , Laederach Alain 
Published: March 2024

AbstractThe SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge. Here, we show by DMS and dual-luciferase functional assays that previously predicted FSE mutants (using the RAG graph theory approach) suppress structural transitions and abolish frameshifting. Furthermore, correlated mutation analysis of DMS data by three programs (DREEM, DRACO, and DANCE-MaP) reveals important differences in their estimation of specific RNA conformations, suggesting caution in the interpretation of such complex conformational landscapes. Overall, the abolished frameshifting in three different mutants confirms that all alternative conformations play a role in the pathways of ribosomal transition.
HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation
Authors: Gendreizig Sarah , Martinez-Ruiz Laura , López-Rodríguez Alba , Pabla Harkiren , Hose Leonie , Brasch Frank , Busche Tobias , Escames Germaine , Sudhoff Holger , Scholtz Lars Uwe , Todt Ingo , Oppel Felix 
Published: March 2024

AbstractHead and neck squamous cell carcinoma (HNSCC) is a highly malignant disease, and death rates have remained at approximately 50% for decades. New tumor-targeting treatment strategies are desperately needed. Using patient-derived tumor cells, we created an HNSCC differentiation model of HPV+ tumor cells from two patients. We observed a loss of malignant characteristics in differentiating cell culture conditions, including irregularly enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. RNA-seq showed myocyte-like differentiation with upregulation of markers of myofibril assembly, including TPM1, TAGLN, and ACTA1. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers reminiscent of myoblast-lineage cells. Moreover, immunofluorescence of HPV+ tumor tissue revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-likein vitrodifferentiation occurs in human tissue. A recent sarcoma study was able to turn rhabdomyosarcoma into muscle-like cells. We are the first to report that carcinoma cells can undergo a triggered myocyte differentiation. Our study suggests that the targeted myo-differentiation of tumor cells might be therapeutically valuable in HPV+ HNSCCs.
Research disturbance negatively impacts incubation behaviour of female Great tits
Authors: Clemencin Léanne , Barba Emilio , Diez-Méndez David 
Published: March 2024

AbstractHuman-induced disturbance is perceived by avian species as a predation risk. However, the anti-predatory behaviour triggered by these non-lethal events can have negative impacts on reproduction and offspring survival. Research on breeding birds often involves visits to their nests and is likely to disrupt parental behaviour, but nest visits that do not involve direct handling of females have been overlooked as important disturbance events. This study focuses on the impacts of short visits to the nest of incubating Great tit(Parus major) females. We investigated how long they stay away from the nest (off-bout) after a disturbance, their possible compensatory behaviour once they resume incubation (on-bout), and the effects on daily incubation rhythms. We used three years of data from two breeding populations to assess the consequences of disturbances in two scenarios: when the female is present in the nest and flushed, and when the female is absent. We found that after a disturbance, the immediate off-bout was longer when the female was either present or absent, with the magnitude of the disturbance being greater when females were flushed. Females did not compensate with longer on-bouts afterwards, i.e. the research disturbance altered daily incubation behaviour by reducing the total time spent on the nest in relation to the number of daily disturbance events. Females that alter their behaviour in response to perceived predation risk would perform longer incubation periods, resulting in lower hatching rates. These effects of research on female behaviour should be considered when planning field experiments.
Evolution of predators and prey kills Turing patterns
Authors: Piskovsky Vit 
Published: March 2024

The spatiotemporal patterns of predators and their prey play a pivotal role in ecology and ecological interactions can drive their formation at fine scales (1). While motility can explain the emergence of such predator-prey patterns (2–14) via the Turing mechanism (15), the predicted Turing patterns do not exhibit temporal changes that are common in experiments (16–24) and nature (25–31). Moreover, the Turing mechanism treats motility as fixed, even though predators and prey adjust their motility in response to each other (32–37) and their interactions influence their evolution (38–47). Using adaptive dynamics (48), I prove that the evolution of motility prevents the formation of Turing patterns and promotes the formation of dynamic patterns, such as predator-prey waves (28, 49–54). The resulting predator-prey cycles are shown to be induced by heterogeneous motility, which extends the emergence of predator-prey cycles beyond regimes predicted by Lotka-Volterra (55) or Rosenzweig-MacArthur (56) models. This work unites models for predator-prey spatiotemporal patterns (2–14) and evolution of motility (57–64) to explain how dynamic spatiotemporal patterns of co-evolving predators and prey emerge and persist. The novel mathematical theory is general and extends to other ecological situations, such as ecological public goods games (65).Significance StatementThe spatio-temporal patterns of predators and their prey play a key role in ecology and are crucial for their conservation. Yet, even at fine scales, such patterns are often complex and exhibit spatial and temporal heterogeneity. While simple mathematical models often predict static spatial patterns (Turing patterns), I show that such patterns of predators and prey are unstable if their motility can evolve. In particular, I suggest that the evolution of motility can give rise to complex spatio-temporal patterns of predators and prey, such as predator-prey waves. Moreover, the mathematical results can be generalised to other contexts, providing novel insights into the evolution of cooperation.
Use of Protein interactions from Imaging Complexes after Translocation (PICT) to characterisein situthe spatial configuration of proteins interacting with the exocyst
Authors: Hernandez Altair C. , Betancur Laura I. , Picco Andrea , Gallego Oriol 
Published: March 2024

ABSTRACTAlthough the structure of the exocyst has been successfully resolved by cryo-electron microscopy, multiple studies showed that exocyst function requires the transient interaction with additional proteins. Unfortunately, the exocyst-interacting network could not be collectively reconstituted, challenging the understanding of how the exocyst complex is coordinated within the network of proteins involved in exocytosis. In a previous work, we described an approach that combines Protein interactions from Imaging Complexes after Translocation (PICT) and centroid localization analysis of diffraction-limited fluorescence signals to estimate the distance between a labelled protein and a spatial reference. This approach allows resolving the spatial organisation of protein interactions directly in living cells, both for intra-complex (i.e. between exocyst subunits) and inter-complex (i.e. between exocyst and transient binding proteins) interactions. In this chapter, we present the protocol to reproduce the sample preparation and image acquisition for PICT experiments. We also describe the computational image analysis pipeline to estimate the distance in PICT experiments. As illustration of the approach, we measure the distance from the spatial reference where the exocyst is anchored to 1) an intra-complex interaction (i.e. Sec5 exocyst subunit) and 2) an inter-complex interaction (Sec2, a guanyl-nucleotide exchange factor mediating vesicle tethering).
Characterizing the expression patterns of short-day flowering genes, the manipulation of their expression using red-far red wavelengths, and the resulting phenotype/ chemotype inCannabis sativa
Authors: Haiden Samuel 
Published: April 2024

AbstractCannabis is a short day (SD) plant whose inflorescences produce valuable medicines. By studying the mechanisms of photoperiodic flowering initiation in cannabis, we may develop new methods of improving cultivation. In SD plants, CONSTANS, which is enhanced by CDL gated proteins that are expressed during short days, acts as a bifunctional regulator of flower inhibition or genesis via FT (florigen). These genes are downstream of phytochrome, which may be activated by horticultural lighting conditions like red (R, 660nm) to far red (FR, 700+nm) wavelength ratios. This study demonstrates that gene expression can be manipulated using high and low R:FR ratios, and characterizes the expression levels of CONSTANS, FT, PRR37, and SOC1 in cannabis over the first 14 short days. It also demonstrates the resulting effect on cannabinoid production and biomass yields.
Microbiome of psyllids of the family Aphalaridae, includingAphalara itadori, a potential biocontrol agent againstReynoutriaspp
Authors: Nishino Kyosuke , Inoue Hiromitsu , Hirose Yuu , Nakabachi Atsushi 
Published: March 2024

AbstractSeveral European and North American countries have started releasing the Japanese knotweed psyllidAphalara itadori(Hemiptera: Aphalaridae) to control the Japanese knotweedReynoutria japonica(Caryophyllales: Polygonaceae) and its relatives, which are among the worst invasive exotic plants. However, establishing populations of the current Kyushu and Hokkaido strains in the field has not been successful, desiring new lineages. Moreover, little is known about the microbiome of the current strains, which potentially impacts properties as biocontrol agents. Hence, this study analyzed the microbiota of anA. itadoristrain newly collected on Honshu Island, along with related species of the family Aphalaridae, using amplicon sequencing of 16S rRNA genes. TheA. itadorisymbionts were further located using fluorescencein situhybridization. The results demonstrated that the analyzedA. itadoristrain has a dual symbiotic system with “CandidatusCarsonella ruddii” (Gammaproteobacteria: Oceanospirillales) andSodalissp. (Gammaproteobacteria: Enterobacterales) harbored in the bacteriome, suggesting their evolutionarily stable mutualistic relationships withA. itadori. The central area of the bacteriome harboringSodalisappeared to comprise uninucleate bacteriocytes with nuclei larger than those of bacteriocytes forCarsonella, rather than a syncytium with smaller nuclei as previously reported for various psyllid lineages. No known plant pathogens or manipulators of insect reproduction were identified in the analyzed strain, indicating its suitability as a biocontrol agent, posing a minimum risk to the ecosystem. Besides distinctCarsonellalineages, the analysis identifiedSodalisindependently acquired byCraspedolepta miyatakeai, and an ambiguousEnterobacteralessymbiont inEpheloscyta kalopanacis. OnlyCarsonellawas identified inTogepsylla matsumurana.