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Biology subjects

Karlsson, K.

Publications and source records attributed to Karlsson, K..

7 recordsLinked to original sources

From video to encounter histories: individual identification and machine vision for salmonid capture-recapture monitoring

Individual encounter histories are central to capture-recapture models, but fisheries monitoring is often reduced to counts that do not account for variation in detection probability. This study presents a machine-vision workflow for converting long-term video surveillance of Atlantic salmon (Salmo salar) and sea trout (Salmo trutta) spawning runs into individual-level data for capture-recapture analysis. The workflow detects fish-positive frames, saves video clips, extracts fish-head regions of interest, and organizes cropped images for re-identification. A binary EfficientNetB0 fish detector achieved validation accuracy of 0.9918 and PR AUC of 0.9992; at a conservative threshold of 0.98, validation false positives were eliminated while retaining 94.3% recall. A YOLOv8n model localized fish-head regions, and an EfficientNetB0 ArcFace model trained on head images from 700 identities achieved 99.80% accuracy among accepted known matches and an image-weighted false-accept rate of 0.81% when non-training identities were treated as unknown. Zero-shot closed-set retrieval achieved 99.17% top-1 accuracy across 1,416 identities excluded from model training, demonstrating strong generalization to previously unseen identities.

ecology↗

De novo Design of Macrocyclic Molecular Glues

The engineering of induced proximity has transformed drug discovery, yet the development of molecular glues remains largely serendipitous and restricted to the retrospective optimisation of accidental discoveries. Here, we present EvoBind-multimer, a deep learning framework for the de novo design of molecular glues directly from protein sequences. Unlike structure-based docking, our method generates small macrocyclic peptides that bridge user-defined protein pairs without requiring prior interface knowledge or existing ligands. We applied this framework to recruit the E3 ligase VHL to two challenging oncoproteins: KRAS and BRD4. Live-cell NanoBRET demonstrated robust design-induced proximity for both pairs. Mechanistic validation demonstrated that the generated macrocycles form functional VHL-target ternary complexes capable of driving Cullin-RING ligase-dependent proteasomal degradation and downstream signalling shutdown. Finally, evaluation in patient-derived xenograft neuroblastoma tumoroids revealed that ternary complex processing is deeply context-dependent: identical macrocycles acted as potent degraders in one patient model, yet functioned as stabilising "LOCKTACs" in another, driving VHL-dependent target sequestration without turnover. By enabling the de novo design of induced proximity from sequence alone, EvoBind-multimer provides a route towards designing new protein functions.

bioinformatics↗

Spatial capture-recapture reveals resource use and declining skipper numbers in Baltic Sea salmon trolling fisheries

Many populations of Atlantic salmon (Salmo salar) native to the Baltic Sea are endangered. A significant group targeting salmon in this region is the recreational trolling fisheries. Due to frequent changes in fisheries regulations and conditions, both the conservation of the species and the fishers are impacted. This study aims to enhance our understanding of the spatial extent and population dynamics of salmon trolling boat skippers in the Baltic Sea by estimating their population size and resource utilization. The study utilizes participation lists of skippers from recreational fishing tournaments and Automatic Identification System (AIS) data to track their movements. These lists are formatted as encounter histories for spatial capture-recapture models, while AIS data are integrated as telemetry data to estimate resource selection. The results reveal a 51% decrease in the number of skippers from two time periods: years 2014-2020 and 2021-2023, with the count dropping from 5,343 individuals (95% CI: 4,622-6,178) to 2,604 individuals (95% CI: 2,273-2,983). The decline may be attributed in part to heavy regulations imposed on recreational salmon fisheries in 2022. Furthermore, the resource selection analysis indicates that these skippers target various species also outside of the Baltic Sea, such as Bluefin tuna (Thunnus thynnus) in Skagerrak, and endangered salmon stocks elsewhere, such as in Lake Vanern. The results of this study suggests that regulations and changes in the Baltic Sea salmon trolling fishery may have broader impacts on seemingly unrelated species and ecosystems.

ecology↗

A microwell platform for high-throughput longitudinal phenotyping and selective retrieval of organoids

Organoids are powerful experimental models for studying the ontogeny and progression of diseases including cancer. Organoids are conventionally cultured in bulk using an extracellular matrix mimic. However, organoids in bulk culture physically overlap, making it impossible to track the growth of individual organoids over time in high throughput. Moreover, local spatial variations in bulk matrix properties make it difficult to assess whether observed phenotypic heterogeneity between organoids results from intrinsic cell differences or microenvironment variability. Here, we developed a microwell-based method that enables high-throughput quantification of image-based parameters for organoids grown from single cells, which can be retrieved from their microwells for sequencing and molecular profiling. Coupled with a deep-learning image processing pipeline, we characterized phenotypic traits including growth rates, cellular movement, and apical-basal polarity in two CRISPR-engineered human gastric organoid models, identifying genomic changes associated with increased growth rate and changes in accessibility and expression correlated with apical-basal polarity.

bioengineering↗

Engineered extracellular matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix (ECM); however, the role that altered cell-ECM signaling may play in driving PDAC phenotype has historically been difficult to dissect. Here, we design an engineered matrix that recapitulates key hallmarks of the tumor ECM and show that patient-derived PDAC organoids develop gemcitabine chemoresistance when cultured within high stiffness matrices mechanically matched to in vivo tumors. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, stiffness-induced chemoresistance occurs due to the development of a plastic cancer stem cell phenotype - mediated by hyaluronan mechanosignaling - with increased expression of drug efflux transporters. Moreover, PDAC chemoresistance is reversible following transfer from high to low stiffness matrices, suggesting that mechanotherapeutics targeting the fibrotic ECM may sensitize chemoresistant tumors. Overall, we demonstrate the power of engineered matrices and patient-derived organoids to elucidate how ECM properties influence human disease pathophysiology.

cancer biology↗

Experimental evolution in TP53 deficient gastric organoids recapitulates tumorigenesis

The earliest events during human tumor initiation, while poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult pre-neoplasia by bi-allelically inactivating TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over two years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single cell sequencing of TP53 deficient gastric organoids similarly indicates progression towards malignant transcriptional programs. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programs repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference, and a striking degree of phenotypic convergence in pre-malignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and reveal evolutionary constraints and barriers to malignant transformation with implications for earlier detection and interception of aggressive, genome instable tumors.

cancer biology↗

Amplification of potential thermogenetic mechanisms in cetacean brains

To elucidate causality underlying the evolution of large brains in cetaceans, we examined the brains of 16 cetartiodactyl species for evidence of non-shivering thermogenesis. In comparison to the artiodactyl brain, the cetacean brain exhibits an expanded expression of uncoupling protein 1 (UCP1, UCPs being mitochondrial inner membrane proteins that dissipate the proton gradient to generate heat) in cortical neurons, localization of UCP4 within a substantial proportion of glia throughout the brain, and an increased density of noradrenergic axonal boutons (noradrenaline functioning to control concentrations of and activate UCPs). Thus, cetacean brains possess multiple characteristics indicative of intensified thermogenetic functionality that can be related to their current and historical obligatory aquatic niche. These findings necessitate reassessment of our concepts regarding the reasons for large brain evolution and associated functional capacities in cetaceans.

neuroscience↗