Biology subjects

Hagen, S.

Publications and source records attributed to Hagen, S..

7 recordsLinked to original sources

bioRxiv2026

Turning an object into a scene: buildings activate scene-selective visual cortex independently of visual features

Human visual cortex contains regions that selectively respond to both scenes and large objects, particularly buildings. The cortical overlap between buildings and scenes has been attributed to shared visual features (e.g., cardinal orientations, rectilinearity). Alternative accounts propose that buildings may also activate scene representations indirectly, independently of specific visual features, for example because buildings evoke a sense of space. Here, we tested for such feature-independent activation by comparing EEG and fMRI responses in human participants (both sexes) to buildings and visually-matched boxes, and relating these responses to scene-selective responses. Buildings and boxes were matched, across exemplars, using image-based metrics, deep neural networks, and a perceptual similarity task. Time-resolved EEG decoding showed that buildings and boxes evoked discriminable responses from 360ms post-stimulus onset, incompatible with feedforward visual feature processing. Importantly, the building-box classifier generalized to discriminate scenes from chairs, providing EEG evidence for a representational overlap between buildings and scenes. Temporal generalization analyses further showed that the late building-selective response corresponded to an earlier scene-selective response, with a temporal offset of [~]130ms. Finally, ultra-fast fMRI (TR=140ms) revealed that these findings were mirrored in the response of the scene-selective parahippocampal place area (PPA), which similarly showed a feature-independent building-selective response that was delayed and prolonged relative to the scene-selective response. These results clarify the nature of building selectivity in visual cortex by showing that this selectivity can arise independently of visual features, putatively reflecting associative processes between buildings and scenes (or space). Significance StatementThe human ventral stream contains regions responding selectively to behaviorally-relevant categories such as places, faces, and words. Contrasting views attribute this selectivity either to the feedforward processing of visual features or to top-down input from domain-specific networks. Here, we show that neural selectivity for buildings persists in the absence of category-diagnostic visual features. EEG decoding showed that this high-level building response emerged late during object processing and corresponded to an earlier scene-selective response. Ultra-fast fMRI revealed that these findings were mirrored in the response of the scene-selective parahippocampal place area (PPA). These results show that selectivity for some categories can be decoupled from visual feature processing, reflecting associative processes that follow object recognition.

neuroscience↗

bioRxiv2026

Dissociating representations of object shape, real-world size, and mobility in human visual cortex

Object representations in the human ventral occipitotemporal cortex (VOTC) are organized along multiple dimensions, including shape (rectilinear vs. curvilinear), real-world size (large vs. small), and mobility (stationary vs. mobile). However, these dimensions are strongly correlated in naturalistic vision, making their separate contributions to VOTC organization unclear. For example, large objects (e.g., a wardrobe, a house) are typically rectilinear and stationary, while small objects (e.g., a ball, a cup) are more curvilinear and mobile. Here, we used fMRI, together with a new stimulus set that orthogonally manipulates shape, size, and mobility, to investigate the separate influences of these dimensions on VOTC organization. Example stimuli include air balloon (large, curvilinear, mobile), radar dish (large, curvilinear, stationary), and mailbox (small, rectilinear, stationary). Contrasts revealed that large (vs. small), rectilinear (vs. curvilinear), and stationary (vs. mobile) dimensions all independently evoked strong and overlapping activity in medio-anterior VOTC. This overlapping activity was at the intersection of the parahippocampal place area (PPA) and the ventral place-memory area (VPMA). Similar results were found at the intersection of the scene-selective occipital place area and the lateral place-memory area (LPMA). Finally, large (vs. small), but not rectilinear (vs. curvilinear) or stationary (vs. mobile) activity, was found in additional posterior ventral scene-selective regions, as well as in early visual cortex. Overall, these results indicate that object shape, real-world size, and mobility dimensions all independently activate scene-selective PPA and OPA, showing joint selectivity for distinct low- and high-level object properties that are highly correlated in naturalistic vision.

neuroscience↗

bioRxiv2025

Super-resolution microscopy reveals a Rab6a-dependent trafficking hub for rhodopsin at the mammalian rod photoreceptor Golgi

Rod photoreceptor stability is critical for retinal health and lifelong vision. The proper intracellular trafficking of the photopigment receptor rhodopsin (Rho) is essential for normal rod homeostasis, as Rho mislocalization precedes rod cell death in inherited retinal disorders such as retinitis pigmentosa. Despite its importance, the molecular mechanisms of Rho trafficking in mammalian rods remain largely undefined. In this study, we combined multiple Rho-labeling strategies with super-resolution microscopy to investigate the subcellular organization of Rho in the Golgi complex of mammalian rods. Using stochastic optical reconstruction microscopy (STORM) and structured illumination microscopy (SIM) super-resolution imaging modalities, we mapped the localization of Golgi proteins with Rho in mouse and macaque rods and found that Rho specifically colocalizes with Rab6a in the trans-Golgi. To test the functional significance of this interaction, we utilized a dominant-negative Rab6a mutant in both HEK293T cells and mouse rods. We demonstrated that the dominant negative Rab6a significantly inhibits Rho secretion in cell culture, causing intracellular retention. In mouse rods, we found that this mutant similarly causes significant Rho retention in the trans-Golgi. However, surprisingly, a majority of Rho protein still escaped the Golgi and reached the outer segment. Together, these findings uncover critical new subcellular details about Rho organization at the Golgi and establish a role for Rab6a as a regulator of Rho protein release from the trans-Golgi in mammalian rods. Our results provide critical insight into the protein trafficking mechanisms that must be sustained and regulated in mammalian rods for long-term retinal health.

cell biology↗

bioRxiv2023

Traditional Norwegian Kveik Yeast: An Ancient Sister Group to Domesticated Saccharomyces cerevisiae

Kveik is the common name of yeast that has been used in traditional farmhouse brewing of western Norway for generations. Its fast fermentation, increased flocculation, temperature tolerance, and rich flavor profile have led to growing interest in recent years. Previous genetic analyses have shown that kveik forms a distinct group within the Saccharomyces cerevisiae tree and placed its origins within the Beer I clade of industrial brewing yeasts, although with signs of mixed ancestry. In this study, we revisited the phylogenetic position of kveik within the S. cerevisiae tree. We searched for traditional farm breweries in western Norway and collected ten samples of potential kveik yeast. Using Illumina whole genome shotgun sequencing, we reconstructed the phylogenetic tree of kveik based on de novo genome assemblies and variant calls of our new kveik samples, along with published wild and domesticated S. cerevisiae strains. We calibrated and used sequential computational experiments at different thresholds to determine the most probable phylogenetic position of kveik yeast. Previously sequenced kveik genotypes form a clade with our new samples clustering partially by place of origin. Our results indicate that kveik is indeed a compact clade within S. cerevisiae with significantly reduced polymorphism compared to common brewing yeasts and wild strains. Contrary to what was previously thought, our analyses support a more ancient divergence of kveik and place it closer to the root of the S. cerevisiae tree. In conclusion, our genetic analyses suggest that kveik is a unique and ancient yeast group, distinct from other domesticated S. cerevisiae strains. Considering a possible far east origin of kveik yeast, the apparent endemism to western Norway remains as a big paradox These findings have important implications for the understanding of yeast domestication and the use of kveik in modern brewing practices.

genomics↗

bioRxiv2020

Dissociated face- and word-selective intracerebral responses in the human ventral occipito-temporal cortex

The extent to which faces and written words share neural circuitry in the human brain is actively debated. Here we compared face-selective and word-selective responses in a large group of patients (N = 37) implanted with intracerebral depth electrodes in the ventral occipito-temporal cortex (VOTC). Both face-selective (i.e., significantly different responses to faces vs. nonface visual objects) and word-selective (i.e., significantly different responses to words vs. pseudofonts) neural activity is isolated through frequency-tagging. Critically, this sensitive approach allows to objectively quantify category-selective neural responses and disentangle them from general visual responses. About 70% of significant contacts show either only face-selectivity or only word-selectivity, with the expected right and left hemispheric dominance, respectively. Spatial dissociations are also found within core regions of face and word processing, with a medio-lateral dissociation in the fusiform gyrus (FG) and surrounding sulci, while a postero-anterior dissociation is found in the inferior occipital gyrus (IOG). Only 30% of the significant contacts show both face- and word-selective responses. Critically, in these contacts, across the VOTC or in the FG and surrounding sulci, between-category selective-amplitudes (faces vs. words) showed no-to-weak correlations, despite strong correlations in both the within-category selective amplitudes (face-face, word-word) and the general visual responses to words and faces. Overall, we conclude that category-selectivity for faces and written words is largely dissociated in the human VOTC. Significance StatementIn modern human societies, faces and written words have become arguably the most significant stimuli of the visual environment. Despite extensive research in neuropsychology, electroencephalography and neuroimaging over the past three decades, whether these two types of visual signals are recognized by similar or dissociated processes and neural networks remains unclear. Here we provide an original contribution to this outstanding scientific issue by directly comparing frequency-tagged face- and word-selective neural responses in a large group of epileptic patients implanted with intracerebral electrodes covering the ventral occipito-temporal cortex. While general visual responses to words and faces show significant overlap, the respective category-selective responses are neatly dissociated in spatial location and magnitude, pointing to largely dissociated processes and neural networks.

neuroscience↗

bioRxiv2019

Species-specific differences in the susceptibility of fungi towards the antifungal protein AFP depend on C3 saturation of glycosylceramides

AFP is an antimicrobial peptide (AMP) produced by the filamentous fungus Aspergillus giganteus and a very potent inhibitor of fungal growth without affecting the viability of bacteria, plant or mammalian cells. It targets chitin synthesis and causes plasma membrane permeabilization in many human and plant pathogenic fungi, but its exact mode of action is not known. We have recently proposed adoption of the \"damage-response framework of microbial pathogenesis\" put forward by Pirofksi and Casadevall in 1999 regarding the analysis of interactions between AMPs and microorganisms, thus, predicting that the cytotoxic capacity of a given AMP is relative and depends not only on the presence/absence of its target(s) in the host and the AMP concentration applied but also on other variables, such as microbial survival strategies. We show here using the examples of three filamentous fungi (Aspergillus niger, Aspergillus fumigatus, Fusarium graminearum) and two yeasts (Saccharomyces cerevisiae, Pichia pastoris) that the important parameters defining the AFP susceptibilities of these fungi are (i) the presence/absence of glycosylceramides, (ii) the presence/absence of {Delta}3(E)-desaturation of the fatty acid chain therein, and (iii) the (dis)ability of these fungi to respond to AFP inhibitory effects with the fortification of their cell walls via increased chitin and {beta}-(1,3)-glucan synthesis. These observations support the adoption of the damage-response framework to holistically understand the outcome of AFP inhibitory effects.\n\nImportanceOur data suggest a fundamental role of glycosylceramides in the susceptibility of fungi towards AFP. We discovered that only a minor structural difference in these molecules - the saturation level of their fatty acid chain, controlled by a 2-hydroxy fatty N-acyl-{Delta}3(E)-desaturase - is a key to understanding the inhibitory activity of AFP. As glycosylceramides are important components of fungal plasma membranes, we propose a model which links AFP-mediated inhibition of chitin synthesis in fungi with its potential to disturb plasma membrane integrity.

microbiology↗

bioRxiv2018

Perturbation of ubiquitin homeostasis promotes macrophage oxidative defenses

Innate immune responses rely on specific pattern recognition receptors that induce downstream signaling cascades and promote inflammatory responses. Emerging evidence suggests that cells may also recognize alterations in cellular processes induced by infection. Protein ubiquitination is a post-translational modification essential for maintaining cellular homeostasis, and infection can cause global alterations in the host ubiquitin proteome. Here we used a chemical biology approach to perturb the cellular ubiquitin proteome as a simplified model to study the direct effect of ubiquitin homeostasis on macrophage responses. We show that perturbation of ubiquitin homeostasis results in a rapid and transient burst of reactive oxygen species (ROS) that promotes macrophage anti-infective capacity. ROS production was dependent on the activity of the phagocyte NADPH oxidase NOX2 and was associated with an increase in intracellular calcium. Our findings suggest that major changes in the host ubiquitin landscape may be a potent signal to rapidly deploy innate immune defenses.

immunology↗