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Kuhn, N.

Publications and source records attributed to Kuhn, N..

6 recordsLinked to original sources

PFOS and GenX Induce Mitochondrial Toxicity and Differentially Alter Respiratory Complex Activities in Liver and Brain

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants associated with adverse health effects, yet the mitochondrial consequences of exposure to individual PFAS and their mixtures remain incompletely understood. This study investigated the individual and combined effects of perfluorooctanesulfonic acid (PFOS) and hexafluoropropylene oxide dimer acid (GenX) on mitochondrial respiratory complex activities under acute, sub-chronic, and chronic exposure conditions. Acute effects were evaluated using isolated mouse liver and brain mitochondria, while repeated exposure was assessed in mice treated with PFOS, GenX, or their combination at 0.2, 2, and 10 mg/kg body weight for 1 month or 0.2 mg/kg for 5 months. PFAS distribution in plasma and brain tissues, mitochondrial oxidative phosphorylation (OXPHOS) protein expression, and predicted interactions with mitochondrial Complexes III and IV were also examined. Acute exposure inhibited Complex III and IV activities, with combined treatment generally producing greater inhibition than either compound alone. Following sub-chronic exposure, mitochondrial responses varied according to dose, treatment, and tissue, with more pronounced reductions in liver complex activities and comparatively limited changes in brain enzyme activities. Chronic low-dose exposure altered selected brain mitochondrial complex activities, while PFAS measurements revealed differences in plasma concentration and distribution across brain regions. OXPHOS protein expression also varied across brain regions and exposure conditions. Molecular docking indicated distinct predicted interaction patterns, with PFOS generally exhibiting more favorable scores at Complex III binding sites and GenX at selected Complex IV regions. Overall, these findings demonstrate exposure-dependent and tissue-specific mitochondrial responses to PFOS and GenX and highlight the importance of evaluating combined PFAS exposure across multiple exposure durations.

pharmacology and toxicology↗

Cooperative processing of visual threat across collicular pathways

Rapid defensive actions require the transformation of sensory cues into appropriate motor responses. The superior colliculus is central to this transformation, containing defined cell-types that form parallel output pathways linking visual inputs to distinct behaviors. However, whether these pathways act independently or cooperate remains unclear. Here we combine cell-type-specific inhibition, large-scale electrophysiology, and functional ultrasound imaging to determine how these pathways contribute to visually evoked defensive behaviors. Inhibiting either narrow-field or wide-field neurons impaired escape to overhead visual threats, demonstrating that both pathways contribute to escape. Recordings from downstream targets revealed a compact representation in the deeper layers of the superior colliculus that selectively distinguished visual stimuli associated with escape, whereas the lateral posterior thalamus contained a broader representation of visual stimuli. The representation of visual threat in the deeper layers of the superior colliculus predicted escape initiation and vigor in freely moving animals. Across the brain, functional ultrasound imaging showed that visual stimuli recruited distinct patterns of activity that could not be explained by response magnitude alone or by the contribution of single cell-types. Together, these results reveal a cooperative circuit architecture in which parallel pathways carry distinct but complementary signals that jointly support visually evoked escape.

neuroscience↗

Sweet signals: Using floral traits to predict nectar sugar availability

Floral nectar is a key energy resource for many animals, yet its availability remains poorly quantified across plant communities. We tested whether floral traits can predict nectar rewards across diverse floras. We analysed relationships between floral morphology and nectar traits in 156 flowering plant species from temperate and tropical regions. Nectar volume, sugar concentration, and total sugar content were measured, and linear mixed-effects models were used to assess floral trait-nectar relationships in tubular and non-tubular flowers. Phylogenetic signal was evaluated using Blombergs K and Pagels {lambda}. Nectar volume increased strongly with corolla size in both floral types. Total sugar content scaled approximately 1:1 with nectar volume despite variation in sugar concentration, indicating that sugar reward is driven primarily by nectar volume. Floral morphology consistently predicted nectar rewards across floras, whereas phylogenetic relatedness explained relatively little variation. These findings provide a scalable framework for estimating floral sugar resources across landscapes.

plant biology↗

Dendritic Architecture Enables de Novo Computation of Salient Motion in the Superior Colliculus

Dendritic architecture plays a crucial role in shaping how neurons extract behaviorally relevant information from sensory inputs. Wide-field neurons in the superior colliculus integrate visual information from the retina to encode cues critical for visually guided orienting behaviors. However, the principles governing how these neurons filter their inputs to generate appropriate responses remain unclear. Using viral tracing, two-photon calcium imaging, and computational modeling, we show that wide-field neurons receive functionally diverse inputs from twelve retinal ganglion cell types, forming a layered, type-specific organization along their dendrites. This structured arrangement allows wide-field neurons to multiplex salient motion cues, selectively amplifying movement and suppressing static features. Computational models reveal that the spatial organization of dendrites and inputs enables the selective extraction of behaviorally relevant stimuli, including de novo computations. Our findings underscore the critical role of dendritic architecture in shaping sensory processing and neural circuit function.

neuroscience↗

Retinal origin of orientation but not direction selective maps in the superior colliculus

Neurons in the mouse superior colliculus ("colliculus") are arranged in ordered spatial maps. While orientationselective (OS) neurons form a concentric map aligned to the center of vision, direction-selective (DS) neurons are arranged in patches with changing preferences across the visual field. It remains unclear if these maps are a consequence of feed-forward input from the retina or local computations in the colliculus. To determine whether these maps originate in the retina, we mapped the local and global distribution of orientation- and direction-selective retinal ganglion cell boutons using in-vivo two-photon calcium imaging. We found that OS boutons formed patches that matched the distribution of OS neurons within the colliculus. DS boutons displayed less regional specializations, better reflecting the organization of DS neurons in the retina. Both eyes convey similar orientation but different DS inputs to the colliculus, as shown in recordings from retinal explants. These data demonstrate that orientation and direction maps within the colliculus are independent, implying that orientation maps are inherited from the retina, but direction maps require local circuits.

neuroscience↗

Transcriptomic and DNA methylation modifications during fruit ripening and in response to ABA treatment in sweet cherry

Abscisic acid (ABA) plays a key role in the ripening process of non-climacteric fruits, triggering pigment production, fruit softening, and sugar accumulation. Transcriptomic studies show that ABA modifies the expression of several ripening-related genes, but to date, the epigenetic approach has not been utilized to characterize the role of ABA during this process. Therefore, this work aimed to perform transcriptomic and DNA methylation analyses of fruit samples treated with ABA during the fruit ripening process in the non-climacteric sweet cherry model. RNA-seq analyses revealed an overrepresentation of transcripts annotated in functional categories related to ABA response, secondary metabolism, and sugar synthesis. In contrast, Whole Genome Bisulfite Sequencing (WGBS) revealed DNA hypomethylation in the 5UTR region of genes related to carotene catabolism. Genes encoding xyloglucan enzymes were regulated transcriptionally and epigenetically during ripening. ABA treatment enhanced color development and ripening. GO analysis of DEGs in the RNA-seq of the ABA treatment revealed expression variations in genes encoding members of the Aux/IAA and ARF families. In the WGBS, genes encoding enzymes of the cytokinin biosynthesis had differential DNA methylation after the ABA treatment. Our work shows the genetic factors modulated by ABA at the genetic and epigenetic levels during non-climacteric ripening.

plant biology↗