Biology subjects

Wurm, M.

Publications and source records attributed to Wurm, M..

12 recordsLinked to original sources

bioRxiv2025

Utilizing CNNs for classification and uncertainty quantification for 15 families of European fly pollinators

Pollination is essential for maintaining biodiversity and ensuring food security, and in Europe it is primarily mediated by four insect orders (Coleoptera, Diptera, Hymenoptera, Lepidoptera). However, traditional monitoring methods are costly and time consuming. Although recent automation efforts have focused on butterflies and bees, flies, a diverse and ecologically important group of pollinators, have received comparatively little attention, likely due to the challenges posed by their subtle morphological differences. In this study, we investigate the application of Convolutional Neural Networks (CNNs) for classifying 15 European pollinating fly families and quantifying the associated classification uncertainty. Our dataset comprises a wide range of morphological and phylogenetic features, such as wing venation patterns and wing shapes. We evaluated the performance of three state-of-the-art CNN architectures, ResNet18, MobileNetV3, and EfficientNetB4, and demonstrate their effectiveness in accurately distinguishing fly families. In particular, EfficientNetB4 achieved an overall accuracy of up to 95.61%. Furthermore, cropping images to the bounding boxes of the Diptera not only improved classification accuracy but also increased prediction confidence, reducing misclassifications among families. This approach represents a significant advance in automated pollinator monitoring and has promising implications for both scientific research and practical applications.

ecology↗

bioRxiv2024

A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should aim to elicit broad-protection, provide long-lasting immunity and facilitate equitable access for all populations. In this study, a panel of chimeric, full-length spike antigens were developed that incorporate mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was obtained from a high-yield production process in stable CHO cells with purity of >95%, long-term stability and elicitation of broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced protein vaccine (NVX-CoV2373), CoVEXS5 could boost T cell immunity, as well as neutralising antibodies levels against viruses from three sarbecoviruses clades. The breadth of sarbecovirus cross-reactivity elicited by CoVEXS5 exceeded that observed after boosting with the NVX-CoV2373 vaccine. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.

immunology↗

bioRxiv2023

Dissociating Goal from Outcome During Action Observation

Understanding the goal of an observed action requires computing representations that are invariant to specific instantiations of the action. For example, we can accurately infer the goal of an action even when the agents desired outcome is not achieved. Observing actions consistently recruits a set of frontoparietal and posterior temporal regions, often labeled the "action observation network" (AON). While progress has been made in charting which regions of the AON, are involved in understanding goals of observed actions, it is not clear where goals are represented independently of outcomes. We used fMRI-based multivariate pattern analysis to identify such regions. Participants watched videos of successful and failed attempts of actions with different goals involving 2 different object types. We found that bilateral anterior inferior parietal lobe and right ventral premotor cortex distinguished between object-specific action goals regardless of outcomes. Left anterior inferior parietal lobe encodes action goals regardless of both outcomes and object types. Our results provide insights into the neural basis of representing action goals and the different roles of frontoparietal and posterior temporal regions in action understanding.

neuroscience↗

bioRxiv2023

Targeting cancer with small molecule pan-KRAS degraders

Despite the high prevalence of cancers driven by KRAS mutations, to date only the G12C mutation has been clinically proven to be druggable via covalent targeting of the mutated cysteine amino acid residue (1). However, in many cancer indications other KRAS mutations, such as G12D and -V, are far more prevalent and small molecule concepts that can address a wider variety of oncogenic KRAS alleles are in high clinical demand (2). Here we show that a single small molecule can be used to simultaneously and potently degrade 13 out of 17 of the most prevalent oncogenic KRAS alleles, including those not yet tractable by inhibitors. Compared with inhibition, degradation of oncogenic KRAS results in more profound and sustained pathway modulation across a broad range of KRAS mutant cell lines. As a result, KRAS degraders inhibit growth of the majority of cancer cell lines driven by KRAS mutations while sparing models without genetic KRAS aberrations. Finally, we demonstrate that pharmacological degradation of oncogenic KRAS leads to tumour regression in vivo. Together, these findings unveil a new path towards addressing KRAS driven cancers with small molecule degraders. One-Sentence SummaryThe most prevalent KRAS variants which drive tumour growth in a major share of cancer patients can be targeted with a single small molecule degrader.

pharmacology and toxicology↗

bioRxiv2022

Precision RNAi using synthetic shRNAmir target sites

Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.

genetics↗

bioRxiv2021

Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens

Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.

microbiology↗

bioRxiv2019

Lateral occipitotemporal cortex encodes perceptual components of social actions rather than abstract representations of sociality

Neuroimaging studies suggest that areas in the lateral occipitotemporal cortex (LOTC) play an important role in the perception of social actions. However, it is unclear what precisely about social actions these areas represent: perceptual features that may be indicative of social actions - such as the presence of persons in a scene, their orientation toward each other, and in particular the directedness of action movements toward persons or other targets - or more abstract representations that capture whether an action is meant to be social. In two fMRI experiments, we used representational similarity analysis (RSA) to test whether LOTC is sensitive to perceptual action components important for social interpretation and/or more general representations of sociality (Experiment 1) and implied person-directedness (Experiment 2). We found that LOTC is sensitive to perceptual action components (person presence, person orientation, and action directedness toward different types of recipients). By contrast, more general levels of sociality and implied person-directedness were not captured by LOTC. Our findings suggest that regions in LOTC provide the perceptual basis for social action interpretation but challenge accounts that posit specialization at more general levels sensitive to social actions and sociality as such. We propose that the interpretation of an action - in terms of sociality or other intentional aspects - arises from the interaction of multiple areas in processing relevant action components in a situation-dependent manner.

neuroscience↗

bioRxiv2019

Individuation of parts of a single object and multiple distinct objects relies on a common neural mechanism in inferior intraparietal sulcus

Object identification and enumeration rely on the ability to distinguish, or individuate, objects from the background. Does multiple object individuation operate only over bounded, separable objects or does it operate equally over connected features within a single object? While previous fMRI experiments suggest that connectedness affects the processing and enumeration of objects, recent behavioral and EEG studies demonstrated that parallel individuation occurs over both object parts and distinct objects. However, it is unclear whether individuation of object parts and distinct objects relies on a common or independent neural mechanisms. Using fMRI-based multivariate pattern analyses, we here demonstrate that activity patterns in inferior and superior intraparietal sulci (IPS) encode numerosity independently of whether the individuated items are connected parts of a single object or distinct objects. Lateral occipital cortex is more sensitive to perceptual aspects of the two stimulus types and the targets of the stimuli, suggesting a dissociation between ventral and dorsal areas in representing perceptual object properties and more general information about numerosity, respectively. Our results suggest that objecthood is not a necessary prerequisite for parallel individuation in IPS. Rather, our results point toward a common individuation mechanism that selects targets over a flexible object hierarchy, independently of whether the targets are distinct separable objects or parts of a single object.

neuroscience↗

bioRxiv2019

The representational space of observed actions

Categorizing and understanding other peoples actions is a key human capability. Whereas there exists a growing literature regarding the organization of objects, the representational space underlying the organization of observed actions remain largely unexplored. Here we examined the organizing principles of a large set of actions and the corresponding neural representations. Using multiple-regression representational similarity analysis of fMRI data, in which we accounted for variability due to major action-related features (body parts, scenes, movements, objects), we found that the semantic dissimilarity structure was best captured by patterns of activation in the lateral occipitotemporal cortex (LOTC) and the left posterior inferior parietal lobe (IPL). Together, our results demonstrate that the organization of observed actions in the LOTC and the IPL resembles the organizing principles used by participants to classify actions behaviorally, in line with the view that these regions are crucial for accessing the meaning of actions.

neuroscience↗

bioRxiv2018

Representation of action concepts in left posterior temporal cortex that generalize across vision and language

Both temporal and frontoparietal brain areas are associated with the representation of knowledge about the world, in particular about actions. However, what these brain regions represent and precisely how they differ remains unknown. Here, we reveal fundamentally distinct functional profiles of lateral temporal and frontoparietal cortex: Using fMRI-based MVPA we found that frontoparietal areas encode representations of observed actions and corresponding written sentences in an overlapping way, but these representations did not generalize across stimulus type. By contrast, only left lateral posterior temporal cortex (LPTC) encoded action representations that generalize across observed action scenes and sentences. The representational organization of stimulus-general action information in LPTC could be predicted from models that describe basic agent-patient relations (object- and person-directedness) and the general semantic similarity between actions. The match between action videos and sentences in LPTC and its representational profile indicate that this region encodes general, conceptual aspects of actions whereas frontoparietal representations appear to be tied to specific stimulus types.

neuroscience↗

bioRxiv2018

Large-scale organization of the hand action observation network in individuals born without hands

The human high-level visual cortex comprises regions specialized for the processing of distinct types of stimuli, such as objects, animals, and human actions. How does this specialization emerge? Here, we investigated the role of sensorimotor experience in shaping the organization of the action observation network as a window on this question. Observed body movements are frequently coupled with corresponding motor codes, e.g. during monitoring ones own movements and imitation, resulting in bidirectionally connected circuits between areas involved in body movements observation (e.g., of the hand) and the motor codes involved in their execution. If the organization of the action observation network is shaped by this sensorimotor coupling, then, it should not form for body movements that do not belong to individuals motor repertoire. To test this prediction, we used fMRI to investigate the spatial arrangement and functional properties of the hand and foot action observation circuits in individuals born without upper limbs. Multivoxel pattern decoding, pattern similarity, and univariate analyses revealed an intact hand action observation network in the individuals born without upper limbs. This suggests that the organization of the action observation network does not require effector-specific visuomotor coupling.

neuroscience↗

bioRxiv2017

Impairment of mitochondrial respiratory function as an early biomarker of apoptosis induced by growth factor removal

Intracellular signaling pathways not only control cell proliferation and survival, but also regulate the provision of cellular energy and building blocks through mitochondrial and non-mitochondrial metabolism. Wild-type and oncogenic RAF kinases have been shown to prevent apoptosis following the removal of interleukin 3 (IL-3) from mouse pro-myeloid 32D cells by reducing mitochondrial reactive oxygen species production. To study primary effects of RAF on mitochondrial energy metabolism, we applied high-resolution respirometry after short-term IL-3 deprivation (8 h), before 32D cells show detectable signs of cell death. Respiration in intact 32D cells was suppressed as an early event following removal of IL-3, but remained more stable in 32D cells expressing the v-RAF oncogene. In permeabilized 32D cells deprived of IL-3, respiratory capacities of the NADH-pathway, the convergent NADH&succinate-pathway, and Complex IV activity were decreased compared to cells grown in the presence of IL-3, whereas succinate-supported respiration remained unchanged, consistent with control by Complex IV. The apparent Complex IV excess capacity was zero above NADH&succinate-pathway capacity reconstituting tricarboxylic acid cycle function. In comparison, electron flow reached only 60% when supported by succinate alone through Complexes II, III and IV, and was therefore relatively insensitive to Complex IV injuries up to a threshold of 40% inhibition. A slight increase in respiration following addition of cytochrome c, a marker of mitochondrial outer membrane leakage, was present after IL-3 depletion, indicating mitochondrial fragility. Our results highlight a novel link between the key mitogenic and survival kinase CRAF and mitochondrial energy homeostasis.

cancer biology↗