Science for Life Laboratory

Design, Synthesis, and Comparative Selection Analysis of a Chemically Diverse Peptide-Like DNA-Encoded Library

Abstract DNA-encoded chemical library technology offers a cost-effective method for screening billions of compounds in a single experiment. However, achieving broad coverage of lead-like chemical space remains challenging. Here, we describe the design and synthesis of a three-cyc...

A supergene and genomic mosaicism are associated with phenotypic evolution in Galápagos tree finches

Abstract Adaptive radiations provide powerful models to study the origins of phenotypic novelty and species diversity. Darwin’s finches constitute a classic example of adaptive radiation, in which beak morphology is a key trait related to fitness. Here, we focus on Camarhynchus t...

Time-lapse RESOLFT nanoscopy empowered by deep learning

Abstract Capturing the dynamic interplay of proteins and organelles within cells requires microscopy methods with high spatial and temporal resolution. Reversible Saturable OpticaL Fluorescent Transition (RESOLFT) demonstrated great potential for live cell nanoscopy by using patt...

Validation of diagnostic artificial intelligence models for prostate pathology in a Middle Eastern cohort

Abstract Artificial intelligence (AI) for pathology is accelerating cancer diagnostics. For global adoption, studies in currently under-represented populations – where the potential gains from AI may also be greatest – are needed. We present the first external validation study in...

Spathology: The Birth of Spatial Pathology as a Discipline

Pathology has always been a spatial science: for more than 150 years, diagnosis has rested on reading the architecture of cells and tissues. Three technological streams are now converging on this founding principle. Spatially resolved omics can measure thousands of transcripts an...

Whole-genome 5-hydroxymethylation profiling of human neurons for regulatory and biological insight

Abstract While 5-methylcytosine (5mC) DNA methylation is a well-known player in genome stability and transcriptional regulation, the role of 5-hydroxymethylcytosine (5hmC), particularly prevalent in neurons, remains largely unknown. Here, we used long-read Oxford Nanopore Technol...

Integrated Multi‐Omics Reveals Cellular States and Microenvironmental Remodeling in Coexisting DCIS and IDC

ABSTRACT Ductal carcinoma in situ (DCIS) is a non‐invasive precursor of invasive ductal carcinoma (IDC), yet the biological mechanisms underlying the transition from DCIS to IDC remain incompletely understood. Here, we integrate spatial transcriptomics, single‐cell RNA sequencing...

Molecular mechanism of complement interference by Streptococcus pyogenes nuclease A

Abstract Bacteria deploy virulence factors to subvert host immunity; yet the molecular details of these interactions often remain limited. Here, we reveal the structure and host interactome of the Streptococcus pyogenes nuclease A (SpnA). We characterize the structure and dynamic...

ABCB1 Frameshift Deletion in Skye Terriers With Potential Pharmacogenetic Relevance

Ivermectin-associated neurotoxicity is a potentially life-threatening condition caused by disruption of the ABCB1 encoded P-glycoprotein drug transporter in certain dog breeds. Skye terriers are considered at increased risk of ivermectin toxicity despite the absence of an identif...

A DPP6 ‐Targeted PET Tracer for Non‐Invasive Imaging of Transplanted Human Islets

ABSTRACT Introduction Dipeptidyl peptidase‐like protein 6 (DPP6) is a potential molecular imaging biomarker for pancreatic and transplanted islets of Langerhans. 4hD29 is a single‐domain antibody with nanomolar affinity for DPP6. Here, we demonstrate the generation and validation...

Adaptive response to serine and glycine deprivation enhances the stemness potential of pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) develops within a nutrient-poor microenvironment, where pancreatic cancer stem cells (PaCSCs) can persist despite limited oxygen and nutrient availability. This resilience partially relies on mitochondrial metabolic flexibility. Serine and...

NheABC is a pH-dependent cytotoxin that targets mitochondria and contributes to the virulence of Bacillus cereus in wound infections

Members of the Bacillus cereus group are Gram-positive, spore-forming, facultative anaerobic bacteria widely distributed in the environment. Pathogenic B. cereus group strains have been linked to a range of illnesses and infections, including severe non-gastrointestinal infection...

Several multiple sequence alignment-perturbing methods enhance AlphaFold3 sampling of alternative protein states

Abstract Protein function often involves multiple conformational states. Several multiple sequence alignment-perturbing strategies, including stochastic subsampling, clustering, and column masking, have been shown to enhance AlphaFold2 (AF2) sampling of alternative protein states...

Identifying drug‐resistant epilepsy using Swedish National Patient Registry data

Abstract Background Approximately 30% of individuals with epilepsy are drug‐resistant, suffering low quality of life and should be evaluated for other treatment modalities. Drug‐resistant epilepsy has no specific diagnostic code, making identification in national healthcare regis...

A review of selected Swedish contributions to instrumentation at neutron scattering facilities

Abstract The European Spallation Source in Lund, Sweden, is the next generation neutron research facility that will provide unprecedented capabilities for particle physics as well as materials and life science research through its high brightness, long-pulse neutron source and ad...

Whole-blood transcriptomics identifies a distinct metabolic and inflammatory signature in lupus arthritis compared with rheumatoid arthritis

BACKGROUND: Lupus arthritis (LA) is a major determinant of clinical outcomes and treat-to-target strategies in systemic lupus erythematosus (SLE), yet its molecular basis remains elusive. METHODS: Whole-blood RNA sequencing from 170 SLE [67 with active arthritis but quiescent dis...

Eco-evolutionary dynamics and environmental detoxification jointly shape bacterial community response to antibiotic perturbation

Microbial communities frequently encounter recurrent antibiotic disturbance, yet how ecological, evolutionary, and environmental processes jointly shape community responses remains unresolved. Here, we use priming to describe the history-dependent effect whereby prior exposure al...

A novel multiomics machine learning signature identifies rapid progression in clinically low risk prostate cancer

Abstract Risk stratification in primary prostate cancer remains heavily reliant on clinicopathological criteria that frequently miss the heterogeneity underlying early aggressive disease. We present a novel machine learning non-linear prognostic framework encoding somatic copy-nu...

Dual screen for gut metabolites suppressing enterobacterial growth and invasiveness reveals structure–activity relationships among anti-infective indoles

The antibiotic resistance crisis has made the characterization of new anti-infective molecules a pressing matter. Molecules that suppress bacterial growth and survival, virulence, or a combination of these traits all warrant further exploration. Naturally occurring microbe‒host e...

Towards a Standard Threshold for Genome Wide Significance in Dogs

ABSTRACT Genome‐wide association studies (GWAS) are a foundational step in tying phenotype to genotype, relying on statistical significance thresholds to distinguish true‐ from false‐positive signals of association. Dog genomics has long relied on per‐study Bonferroni thresholds...