bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative fMRI reveals differences in the functional organization of the visual cortex for animacy perception in dogs and humans
Authors: Farkas Eszter Borbála , Hernández-Pérez Raúl , Cuaya Laura Veronica , Rojas-Hortelano Eduardo , Gácsi Márta , Andics Attila 
Published: November 2024

AbstractThe animate-inanimate category distinction is one of the general organizing principles in the primate high-level visual cortex. Much less is known about the visual cortical representations of animacy in non-primate mammals with a different evolutionary trajectory of visual capacities. To compare the functional organization underlying animacy perception of a non-primate to a primate species, here we performed an fMRI study in dogs and humans, investigating how animacy structures neural responses in the visual cortex of the two species. Univariate analyses identified animate-sensitive bilateral occipital and temporal regions, non-overlapping with early visual areas, in both species. Multivariate tests confirmed the categorical representations of animate stimuli in these regions. Regions sensitive to different animate stimulus classes (dog, human, cat) overlapped less in dog than in human brains. Together, these findings reveal that the importance of animate-inanimate distinction is reflected in the organization of higher-level visual cortex, also beyond primates. But a key species difference, that neural representations for animate stimuli are less concentrated in dogs than in humans suggests that certain underlying organizing principles that support the visual perception of animacy in primates may not play a similarly important role in other mammals.
Temperature and dissolved organic matter shape marine prokaryotic activity and gene expression in a sub-arctic sea
Authors: Amnebrink Dennis , Verma Ashish , Lundin Daniel , Wikner Johan , Pinhassi Jarone 
Published: November 2024

AbstractTemperature and dissolved organic matter (DOM) are important drivers of microbial activity, but their effects, alone or in combination, on the physiological responses of sub-arctic prokaryotic assemblages remain poorly understood. In a northern Baltic Sea one-month mesocosm experiment, we therefore exposed a coastal microbial community to temperature and nutrient regimes representative of winter and early summer (i.e., 1°C and 10°C, with and without DOM additions) in a 2×2 factorial design. Midway through the experiment, specific growth rates were highest for the 10°C plus DOM treatment (TN; ∼2.5 day-1), comparable for the 1°C plus DOM (N) and the 10°C (T) treatments at ∼1.0 day-1; and low for the control (1°C, no DOM enrichment [C]; 0.2 day-1). Taxonomic analysis of metatranscriptomes uncovered broad treatment specific responses, and a PERMANOVA on the 182,618 transcribed genes revealed statistically significant effects of both temperature and DOM, and significant interaction effects between the two (altogether involving 18% of genes). Significant differences in transcription identified by EdgeR analysis includedNitrosopumilusgenes for ammonium uptake and ammonia oxidation in the 1°C mesocosms (C, N), membrane transporters for small organic acids in the N-treatment, genes for nitrogen and phosphorus assimilation along with molecular chaperones in the T-treatment, and dominance of Oceanospirillales genes for energy and growth metabolism in the TN-treatment. These metatranscriptomic responses were associated with changes in e.g. prokaryotic growth rates and growth efficiency, providing clues to how successional changes in community composition and metabolism are directed by temperature and DOM as central factors underlying environmental change.ImportanceIt is recognized that increases in temperature and dissolved organic matter loading are key to understanding how climate change will influence polar ecosystems. Still, little is known of the effects of these factors on the physiological responses of Arctic prokaryotes. Since prokaryotes are principal drivers of biogeochemical cycles, we investigated how temperature and dissolved organic matter influence prokaryotic transcriptional responses in taxonomy and metabolic pathways. The metatranscriptomics analyses uncovered broad treatment specific responses linked with changes in prokaryotic community composition, growth rates, and growth efficiency. Yet, and importantly, the expression of most metabolic functions remained stable, suggesting a pronounced functional resilience of the prokaryotic community enabled by shifts in the dominance of different taxa. This emphasizes the large potential and importance of identifying the metabolic functions that underlie the divergence of prokaryotic communities in response to environmental changes projected to alter some of the most vulnerable marine environments.
Enhanced Intestinal Epithelial Co-Culture Model with Orbital Mechanical Stimulation: A Proof-of-Concept Application in Food Nanotoxicology
Authors: Santoni Mattia , Piccinini Giovanni , Liguori Giovanni , Randi Maria Roberta , Baroncini Massimo , Milani Liliana , Danesi Francesca 
Published: November 2024

AbstractIntroductionCurrent in vitro intestinal models lack the mechanical forces present in the physiological environment, limiting their reliability for nanotoxicology studies. Here, we developed an enhanced Caco-2/HT29-MTX-E12 co-culture model incorporating orbital mechanical stimulation to better replicate intestinal conditions and investigate nanoparticle interactions.MethodsWe established co-cultures under static and dynamic conditions, validating their development through multiple approaches including barrier integrity measurements, gene expression analysis, and confocal microscopy. We introduced novel quantitative analysis of dome formation as a differentiation marker and demonstrated the model application by investigating cellular responses to titanium dioxide (TiO) nanoparticles in a digested food matrix.ResultsDynamic conditions accelerated epithelial differentiation, achieving functional barrier properties by day 14 rather than day 21, with enhanced mucin production and more organized three-dimensional structure. Mechanical stimulation selectively promoted goblet cell differentiation without affecting general epithelial markers. The optimized model successfully detected concentration-dependent oxidative stress responses to TiO exposure, revealing cellular dysfunction preceding membrane damage.DiscussionThis improved co-culture system provides a better physiological platform for nanotoxicology studies. By incorporating mechanical forces, each cell type exhibits more representative behavior, creating a more realistic experimental setup. The model bridges the gap between simple monocultures and complex 3D systems, offering a practical approach for investigating nanoparticle-epithelium interactions in a food-relevant context.
Cerebellar white matter development is regulated by fractalkine-dependent microglia phagocytosis of oligodendrocyte progenitor cells
Authors: Chappell McKenzie K. , Shelestak John , Irfan Muhammad , Shelestak Eric , Nemes-Baran Ashley D. , Mey Gabrielle M. , DeSilva Tara M. 
Published: November 2024

SummaryComplex neurodevelopmental disorders involve motor as well as cognitive dysfunction and these impairments are associated with both cerebral and cerebellar maturity. A network of connections between these two brain regions is proposed to underlie neurodevelopmental impairments. The cerebellar gray matter has a protracted developmental timeline compared to the cerebral cortex, however, making the association of these relay pathways unclear for neurodevelopmental disabilities. We show that a population of amoeboid microglia infiltrate the cerebellar white matter through the fourth ventricular zone during early postnatal development. This infiltration is synchronized with the emergence of amoeboid microglia in the ventricular zone of the lateral ventricles and appearance in cerebral white matter. Amoeboid microglia phagocytosed oligodendrocyte progenitor cells (OPCs) in the cerebellar white matter during a restricted early postnatal time window before transitioning to a ramified morphology. Modulating fractalkine receptor signaling, shown to be involved in microglial pruning of synapses, significantly reduced microglial engulfment of OPCs resulting in increased numbers of OLs and altered myelin formation. Variants in the fractalkine receptor are associated with neurodevelopmental disorders including schizophrenia and autism where myelin perturbations have been documented. Overall, these data support that white matter refinement by amoeboid microglia is coordinated in both cerebral and cerebellar development with important implications for altered circuit function in neurodevelopmental disabilities.One sentence summaryMicroglia engulf oligodendrocyte progenitors in the developing cerebellum
Calmodulin acts as a chaperone during co-translational folding of the Kv7.2 channel Calcium Responsive Domain
Authors: Muguruza-Montero Arantza , Tait Jack R. , M-Alicante Sara , Metola Ane , Nuñez Eider , Urrutia Janire , Sunderlíková Vanda , Katranidis Alexandros , von Heijne Gunnar , Tans Sander J. , Villarroel Alvaro 
Published: November 2024

AbstractIn vivo, the majority of nascent protein chains must begin folding during translation in order to obtain their native structure. While the importance of co-translational folding has become increasingly clear, the specific mechanisms underlying the coordination between the ribosome, nascent chain and molecular chaperones are still uncertain. Here, we have constructed a model of the co-translational folding pathway of the calcium responsive domain (CRD) of the human neuronal KV7.2 human neuronal ion channel, showing that calmodulin (CaM) is crucial. By combining Force Profile Analysis and single-molecule force spectroscopy techniques, we found that CaM, in a calcium-dependent manner, affects early folding events involving three key α-helices in the CRD. In addition, this study suggests that CaM at early stages induces the formation of metastable hairpins, as a part of the co-translational folding pathway. These findings expand on the role of CaM as a key regulator of folding in eukaryotes: not only as an essential cellular signaling protein, but also as abona fideco-translational molecular chaperone.
Postnatal maturation of serotonergic modulation of spinal RORβ interneurons in the medial deep dorsal horn
Authors: West Christopher W. , Garcia-Ramirez D. Leonardo , Dougherty Kimberly J. 
Published: November 2024

AbstractProprioceptive input is essential for coordinated locomotion and this input must be properly gated to ensure smooth and effective movement. Presynaptic inhibition mediated by GABAergic interneurons provides regulation of sensory afferent feedback. Serotonin not only promotes locomotion, but also modulates feedback from sensory afferents, both directly and indirectly, potentially by acting on the GABAergic interneurons that mediate presynaptic inhibition. Developmental disruptions in presynaptic inhibition can produce deficits in sensorimotor processing. Importantly, both presynaptic inhibition of proprioceptive afferents and serotonergic innervation of the spinal cord become mature and functional after the first postnatal week. However, little is known about the serotonergic receptors involved in the modulation of interneurons mediating presynaptic inhibition and when developmentally their actions mature. Here, we used whole-cell patch clamp recordings in lumbar spinal slices from neonatal and juvenile mice to assess the intrinsic properties and serotonergic modulation of deep dorsal horn GABAergic RORβ interneurons previously shown to mediate presynaptic inhibition of proprioceptive afferents. RORβ interneurons from juvenile cords displayed more mature membrane properties. Further, serotonin increased the excitability of RORβ interneurons via actions at 5-HT2A, 5-HT2B/2C, and 5-HT7receptors in juvenile but not early neonatal spinal cords. Our findings indicate that deep dorsal horn RORβ interneurons undergo postnatal maturation in both their intrinsic excitability and ability to respond to serotonin, concurrent with the maturation of serotonergic innervation of the dorsal horn. This information can prompt future targeted studies testing relationships between impairments of serotonergic development, proprioceptive processing disorders, and presynaptic inhibition mediated by RORβ interneurons.
Brain-region-specific changes and dysregulation of activity regulated genes inGria3mutant mice, a genetic animal model of schizophrenia
Authors: Huang Wei-Chao , Kast Ryan , Mandell Kira Perzel , Dejanovic Borislav , Bonanno Kevin , Aryal Sameer , Farsi Zohreh , Wilde Jonathan , Wang Dongqing , Gao Xian , Keshishian Hasmik , Carr Steven A. , Feng Guoping , Sheng Morgan 
Published: November 2024

ABSTRACTProtein-truncating variants inGRIA3(encoding the GluA3/GluR3 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors) are associated with substantially increased risk of schizophrenia (SCZ). Here we characterizedGria3mutant mice carrying a protein-truncating mutation that mimics a SCZ-associated variant. Transcriptomic analysis revealed that activity-regulated genes are downregulated in cortical regions, while immune and glia-related pathways exhibit brain-region-specific changes. The transcriptomic changes inGria3mutant mice are remarkably different from those inGrin2amutant mice, particularly in the prefrontal cortex, even though both encode glutamate receptors and are associated with SCZ risk. Proteomic analysis further demonstrated that loss-of-function ofGria3profoundly alters the protein composition of synapses. These findings in a genetic mouse model provide potential insights into the pathophysiological mechanisms underlying SCZ.
N-formylkynurenine but not kynurenine enters a nucleophile-scavenging branch of the immune-regulatory kynurenine pathway
Authors: Wang Yongxin , Leung Euphemia , Tomek Petr 
Published: November 2024

AbstractTryptophan catabolism along the kynurenine pathway (KP) mediates key physiological functions ranging from immune tolerance to lens UV protection, but the contributory roles and chemical fates of individual KP metabolites are incompletely understood. This particularly concerns the first KP metabolite, N-formylkynurenine (NFK), canonically viewed as a transient precursor to the downstream kynurenine (KYN). Here, we challenge that canon and show that hydrolytic enzymes act as a rheostat switching the fate of NFK between the canonical KP and a novel non-enzymatic branch of tryptophan catabolism.In the physiological environment (37°C, pH 7.4), NFK deaminated into electrophilic NFK- carboxyketoalkene (NFK-CKA), which rapidly (< 2 minutes) formed adducts with nucleophiles such as cysteine and glutathione, the key intracellular antioxidants. Serum hydrolases suppressed NFK deamination as they hydrolysed NFK to KYN ∼3 times faster than NFK deaminates. Whilst KYN did not deaminate, its deaminated product (KYN-CKA) rapidly reacted with cysteine but not glutathione.The new NFK transformations of yet to be confirmed functions highlight significance of NFK beyond hydrolysis to KYN and suggests the dominance of its chemical transformations over those of KYN in physiological environments. Enzyme compartmentalisation and abundance offer insights into the regulation of non-enzymatic NFK and KYN transformations that are emerging as contributors to immune regulation, protein modification, lens aging or neuropathology.
Integration of cortical inputs in the lateral hypothalamus is dominated by the medial prefrontal cortex
Authors: Razenberg L.J.A.M. , de Greef P.N. , Mansvelder H.D. , Karnani M.M. 
Published: November 2024

AbstractThe lateral hypothalamus (LH) is a critical brain region orchestrating survival behaviours including feeding. Its sparse intrinsic synaptic connectivity allows long-range projections to modulate its activity. Some of these projections arise from the cerebral cortex, which is known to influence feeding. However, the functional and anatomical organization of cortico-hypothalamic pathways have remained poorly studied. We used anatomical and optogenetic mapping to show that the medial prefrontal cortex (mPFC) is the strongest cortical input source to the LH, followed by a lateral associative region including the insular cortex (IC), and the ventral subiculum. Input from the mPFC and IC had markedly different synaptic dynamics and were integrated supralinearly. IC input surpassed that of the mPFC in a subpopulation of highly excitable dorsal LH neurons which had a strong h-current. Input from the mPFC showed selective targeting to LH neurons which project back to the mPFC, suggesting the existence of a direct feedback loop. Overall, these results identify a direct prefrontal hypothalamic pathway which is poised to dominate rapid cortical control of hypothalamic activity.
Natural variations ofTaMYB7-A1regulate PHS resistance and specify wheat geographic adaptation
Authors: Wang Hao , Wang Dongzhi , Guo Yafei , Zhang Min , Simmonds James , Zheng Qi , Hou Jian , Liu Xuemei , Lin Xuelei , Bie Xiaomin , Zhang Xiansheng , Zhang Xueyong , Uauy Cristobal , Lu Fei , Chu Chengcai , Tian Zhixi , Xiao Jun 
Published: November 2024

AbstractCrop domestication tended to select against seed dormancy for uniform germination—raising risks of undesirable pre-harvest sprouting (PHS) — but regulation of seed dormancy and PHS in wheat are grossly under-characterized. Here, we identified wheat PHS resistance loci by GWAS.TaMYB7-A1confers PHS resistance by elevating ABA signaling and seed dormancy in grains. ThreeTaMYB7-A1haplotypes (Hap-1/2/3) contrast in PHS resistance, with Gly23 and Gly92 crucial for binding to and activatingTaABI5in Hap-1/3. A MITE transposon in theTaMYB7-A1Hap-1promoter likely recruited the TaAZF1–TaABI4 module to boost expression, resulting in strong PHS resistance.TaMYB7-A1Hap-1originated from wild einkorn and was integrated into hexaploid wheat through introgression into wild emmer. Different haplotypes ofTaMYB7-A1,in conjunction with alleles of other major PHS resistance genes, is pivotal in shaping wheat’s adaptability to rainfall conditions in China, US and Europe during the harvest season. Introduction ofTaMYB7-A1Hap-1into elite cultivars confers PHS resistance without yield defects. Thus, artificial and natural selection across diverse climates regions have collectively shaped wheat adaptation and enabled rational delivery of improved lines tailored to local cropping needs.
Uncovering dynamic human brain phase coherence networks
Authors: Olsen Anders S. , Brammer Anders , Fisher Patrick M. , Mørup Morten 
Published: November 2024

ABSTRACTComplex behavioral and cognitive processes emerge from coordinated communication between sometimes disparate brain regions, implying a systems-level dynamic synchronization of underlying neural signals. This study presents approaches to multivariate mixture modeling of functional brain imaging data for analyzing phase coherence networks for human brain macroscale dynamic functional connectivity. We show that 1) the complex domain is required to analyze phase coherence in its entirety, 2) statistical models for complex-valued phase coherence, particularly the complex angular central gaussian (ACG) distribution, greatly exceeds performance over models for time-series data, rank-2 cosine phase coherence maps, or the leading eigenvector of cosine phase coherence maps (i.e., LEiDA), 3) methods should account for the inherent anisotropy of the brain’s interconnections. We emphasize the need to utilize models that account for the manifold on which the data reside, and show that the proposed models provide valuable information about intrinsic functional connectivity networks and can easily distinguish task-related brain function. We provide an open-source, Python-based toolbox (“Phase Coherence Mixture Modeling” (PCMM):github.com/anders-s-olsen/PCMM) to facilitate and promote implementation of these models.
Soil viral and prokaryotic communities shifted significantly after wildfire in chaparral and woodland habitats
Authors: Geonczy Sara E. , ter Horst Anneliek M. , Emerson Joanne B. 
Published: November 2024

ABSTRACTIncreased wildfire activity warrants more research into fire-driven biotic changes in soil, given that soil microbes contribute to biogeochemical processes by way of organic matter decomposition, nutrient cycling, and promoting plant growth. Viruses of prokaryotes apply pressure to microbial communities, making their responses to fire also important for understanding post-fire ecology. Leveraging viromes and 16S rRNA gene amplicon sequencing, here we studied viral and prokaryotic community responses to wildfire in woodland and chaparral soils at five timepoints over one year following the California LNU Complex wildfire.We also compared post-fire samples to unburned controls at the final three timepoints, beginning five months after the fire. Viromic DNA yields were low-to-undetectable (indicative of low viral particle abundances), particularly for the first post-fire timepoint, and comparisons to controls suggest a return to baseline viral particle abundances within five months of the wildfire. Viral and prokaryotic community composition and soil chemistry differed significantly in burned samples compared to controls from both habitats. Compared to controls, a greater proportion of viral ‘species’ (vOTUs) from a burned conifer forest were detected in both burned habitats here, suggesting fire-associated habitat filtering. Published viromes collected from the same sites nine months pre-fire were more similar to controls than to post-fire viromes. Together, these results indicate significant changes in soil viral and prokaryotic communities due to wildfire.
Early exercise disrupts a pro-repair extracellular matrix program during zebrafish fin regeneration
Authors: Lewis Victor M. , Fernandez Rafael A. , Horst Samuel G. , Stankunas Kryn 
Published: November 2024

AbstractUnderstanding how mechanical stimulation from exercise influences cellular responses during tissue repair could enhance therapeutic strategies. We explored zebrafish caudal fin regeneration to study exercise impacts on a robust model of tissue regeneration. We used a swim tunnel to determine that exercise initiated during but not after blastema establishment impaired fin regeneration, including of the bony ray skeleton. Long-term tracking of fluorescently labeled cell lineages showed exercise disrupted blastemal mesenchyme formation. Transcriptomic profiling and section staining indicated exercise reduced an extracellular matrix (ECM) gene expression program, including for hyaluronic acid (HA) synthesis. Like exercise, HA synthesis inhibition or blastemal HA depletion disrupted blastema formation. We considered if injury-upregulated HA establishes a pro-regenerative environment facilitating mechanotransduction. HA density across the blastema correlated with nuclear localization of the mechanotransducer Yes-associated protein (Yap). Further, exercise loading or reducing HA decreased nuclear Yap and cell proliferation. We conclude early exercise during fin regeneration disrupts expression of an HA-rich ECM supporting blastema expansion. These results highlight the interface between mechanotransduction and ECM as consideration for timing exercise interventions and developing regenerative therapies.Significance StatementControlled exercise promotes healing and recovery from severe skeletal injuries. However, properly timed interventions are essential to promote recovery and prevent further damage. We use zebrafish caudal fin regeneration to mechanistically study exercise impacts on a naturally robust and experimentally accessible model of tissue repair. We link detrimental early exercise effects during fin regeneration to impaired ECM synthesis, mechanotransduction, and cell proliferation. These insights could explain the value of delaying the onset of physical therapy and suggest pursuing therapies that maintain ECM integrity for regenerative rehabilitation.