Mammalian cell-based production of glycans, glycopeptides and glycomodules.

Access to defined glycans and glycoconjugates is pivotal for discovery, dissection, and harnessing of a range of biological functions orchestrated by cellular glycosylation processes and the glycome. We previously employed genetic glycoengineering by nuclease-based gene editing to develop sustainable production of designer glycoprotein therapeutics and cell-based glycan arrays that display glycans in their natural context at the cell surface. However, access to human glycans in formats and quantities that allow structural studies of molecular interactions and use of glycans in biomedical applications currently rely on chemical and chemoenzymatic syntheses associated with considerable labor, waste, and costs.

Proteome characterization of extracellular vesicles from human milk: Uncovering the surfaceome by a lipid-based protein immobilization technology.

Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex fluid is rich in extracellular vesicles (EVs). Here, we have applied a microfluidic technology, lipid-based protein immobilization (LPI) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) to characterize the proteome of human milk EVs.

Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.

Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes.

Surface-Shaving of Strains and Quantitative Proteomic Analysis Reveal Differences in Protein Abundance of the Surfaceome.

is a pathogen known to cause a wide range of infections. To find new targets for identification and to understand host-pathogen interactions, many studies have focused on surface proteins. We performed bacterial-cell surface-shaving, followed by tandem mass tag for quantitative mass spectrometry proteomics, to examine the surfaceome of .

Exophiala species in household environments and their antifungal resistance profile.

The black fungus Exophiala causes a wide range of infections from superficial to subcutaneous, but also invasive fungal infections in immunocompromised patients as well as healthy individuals. In addition, Exophiala, is a common colonizer of the air ways of patients with cystic fibrosis. However, the source of infection and mode of transmission is still unclear.

Open-Vocabulary Predictive World Models from Sensor Observations.

Cognitive scientists believe that adaptable intelligent agents like humans perform spatial reasoning tasks by learned causal mental simulation. The problem of learning these simulations is called predictive world modeling. We present the first framework for a learning open-vocabulary predictive world model (OV-PWM) from sensor observations.

El Hierro Genome Study: A Genomic and Health Study in an Isolated Canary Island Population.

El Hierro is the smallest and westernmost island of the Canary Islands, whose population derives from an admixture of different ancestral components and that has been subjected to genetic isolation. We established the "El Hierro Genome Study" to characterize the health status and the genetic composition of ~10% of the current population of the island, accounting for a total of 1054 participants. Detailed demographic and clinical data and a blood sample for DNA extraction were obtained from each participant.

Exposing kinetic disparities between inflammasome readouts using time-resolved analysis.

The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1β and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others.

Association of Occupational Dysfunction and Hospital Admissions With Different Polygenic Profiles in Bipolar Disorder.

Objective: Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles.

The genetic architecture of dog ownership: large-scale genome-wide association study in 97,552 European-ancestry individuals.

Dog ownership has been associated with several complex traits, and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through a meta-analysis of 31,566 Swedish twins in 5 discovery cohorts and an additional 65,986 European-ancestry individuals in 3 replication cohorts from Sweden, Norway, and the United Kingdom. Association tests with >7.

R-Cut: Enhancing Explainability in Vision Transformers with Relationship Weighted Out and Cut.

Transformer-based models have gained popularity in the field of natural language processing (NLP) and are extensively utilized in computer vision tasks and multi-modal models such as GPT4. This paper presents a novel method to enhance the explainability of transformer-based image classification models. Our method aims to improve trust in classification results and empower users to gain a deeper understanding of the model for downstream tasks by providing visualizations of class-specific maps.

Structure and function of Semaphorin-5A glycosaminoglycan interactions.

Integration of extracellular signals by neurons is pivotal for brain development, plasticity, and repair. Axon guidance relies on receptor-ligand interactions crosstalking with extracellular matrix components. Semaphorin-5A (Sema5A) is a bifunctional guidance cue exerting attractive and inhibitory effects on neuronal growth through the interaction with heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs), respectively.

Notes from Beethoven's genome.

Rapid advances over the last decade in DNA sequencing and statistical genetics enable us to investigate the genomic makeup of individuals throughout history. In a recent notable study, Begg et al. used Ludwig van Beethoven's hair strands for genome sequencing and explored genetic predispositions for some of his documented medical issues.

Key subphenotypes of bipolar disorder are differentially associated with polygenic liabilities for bipolar disorder, schizophrenia, and major depressive disorder.

Bipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577).

MiCId GUI: The Graphical User Interface for MiCId, a Fast Microorganism Classification and Identification Workflow with Accurate Statistics and High Recall.

Although many user-friendly workflows exist for identifications of peptides and proteins in mass-spectrometry-based proteomics, there is a need of easy to use, fast, and accurate workflows for identifications of microorganisms, antimicrobial resistant proteins, and biomass estimation. Identification of microorganisms is a computationally demanding task that requires querying thousands of MS/MS spectra in a database containing thousands to tens of thousands of microorganisms. Existing software can't handle such a task in a time efficient manner, taking hours to process a single MS/MS experiment.

Dissecting the impact of complement component 4A in bipolar disorder.

The genetic overlap between schizophrenia (SZ) and bipolar disorder (BD) is substantial. Polygenic risk scores have been shown to dissect different symptom dimensions within and across these two disorders. Here, we focused on the most strongly associated SZ risk locus located in the extended MHC region, which is largely explained by copy numbers of the gene coding for complement component 4A (C4A).

Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans.

Chemokine-driven leukocyte recruitment is a key component of the immune response and of various diseases. Therapeutically targeting the chemokine system in inflammatory disease has been unsuccessful, which has been attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies.