A5013361951- Biomedical Text Mining and Ontologies
- Topic Modeling
- RNA and protein synthesis mechanisms
- Semantic Web and Ontologies
- Mitochondrial Function and Pathology
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Speech and dialogue systems
- Photoreceptor and optogenetics research
- Protein Structure and Dynamics
- Neuroscience and Neural Engineering
- Natural Language Processing Techniques
- Recommender Systems and Techniques
- Pluripotent Stem Cells Research
- Advanced Bandit Algorithms Research
- Enzyme Structure and Function
- Viral Infectious Diseases and Gene Expression in Insects
- Image Retrieval and Classification Techniques
- Cardiac electrophysiology and arrhythmias
- Insect Resistance and Genetics
- Cardiomyopathy and Myosin Studies
- Chemical Synthesis and Analysis
- Microbial Metabolic Engineering and Bioproduction
- Consumer Market Behavior and Pricing
- Social Sciences and Governance
University of Zurich
2016-2024
University of Minnesota
2023-2024
University of Alabama at Birmingham
2017-2024
Amazon (Germany)
2020-2023
University of Minnesota System
2023
Max Planck Institute for Informatics
2013-2019
Max Planck Society
2015-2019
Daewoong Pharmaceutical (South Korea)
2017
Johns Hopkins University
2017
University of Pennsylvania
2017
Abstract TDP-43 is a primarily nuclear RNA-binding protein, whose abnormal phosphorylation and cytoplasmic aggregation characterizes affected neurons in patients with amyotrophic lateral sclerosis frontotemporal dementia. Here, we report that physiological mouse human brain forms homo-oligomers are resistant to cellular stress. Physiological oligomerization mediated by its N-terminal domain, which can adopt dynamic, solenoid-like structures, as revealed 2.1 Å crystal structure combination...
Highlights•Adaptation of Listeria phage serovar specificity through targeted RBP variations•High-resolution crystal structure a receptor binding protein•Structure-guided design chimeras yields phages with predictable host ranges•Synthetic RBPs extend (from SV 4b to 4a, 4b, 4d, 5, 6b)SummaryBacteriophages provide excellent tools for diagnostics, remediation, and microbiome manipulation, yet isolating viruses suitable remains challenging. Using PSA, we present synthetic biology blueprint...
Biomedical knowledge bases (KB's) have become important assets in life sciences. Prior work on KB construction has three major limitations. First, most biomedical KBs are manually built and curated, cannot keep up with the rate at which new findings published. Second, for automatic information extraction (IE), text genre of choice been scientific publications, neglecting sources like health portals online communities. Third, prior IE focused molecular level or chemogenomics only,...
Most systemic viral gene therapies have been limited by sequestration and degradation of virions, innate adaptive immunity, silencing therapeutic genes within the target cells. Here we engineer a high-affinity protein coat, shielding most commonly used vector in clinical therapy, human adenovirus type 5. Using electron microscopy crystallography demonstrate massive coverage virion surface through hexon-shielding scFv fragment, trimerized to exploit hexon symmetry gain avidity. The shield...
Knowledge bases (KB's) contribute to advances in semantic search, Web analytics, and smart recommendations. Their coverage of domain-specific knowledge is limited, though. This demo presents the KnowLife portal, a large KB for health life sciences, automatically constructed from sources. Prior work on biomedical ontologies has focused molecular biology: genes, proteins, pathways. In contrast, one-stop portal much wider range relations about diseases, symptoms, causes, risk factors, drugs,...
Abstract Green fluorescent protein (GFP) fusions are pervasively used to study structures and processes. Specific GFP-binders thus of great utility for detection, immobilization or manipulation GFP-fused molecules. We determined two designed ankyrin repeat proteins (DARPins), complexed with GFP, which revealed different but overlapping epitopes. Here we show a structure-guided design strategy that, by truncation computational reengineering, led stable construct where both can bind...
Neurotensin receptor 1 (NTSR1) and related G protein-coupled receptors of the ghrelin family are clinically unexploited, several mechanistic aspects their activation inactivation have remained unclear. Enabled by a new crystallization design, we present five structures: apo-state NTSR1 as well complexes with nonpeptide inverse agonists SR48692 SR142948A, partial agonist RTI-3a, novel full SRI-9829, providing structural rationales on how ligands modulate NTSR1. The favor large extracellular...
Abstract The receptor tyrosine kinase HER2 acts as oncogenic driver in numerous cancers. Usually, the gene is amplified, resulting overexpression, massively increased signaling and unchecked proliferation. However, tumors become frequently addicted to oncogenes hence are druggable by targeted interventions. Here, we design an anti-HER2 biparatopic tetravalent IgG fusion with a multimodal mechanism of action. molecule first induces clustering into inactive complexes, evidenced reduced...
Rationale:The conserved long non-coding RNA (lncRNA) myocardial infarction associate transcript (Miat) was identified for its multiple single-nucleotide polymorphisms that are strongly associated with susceptibility to MI, but role in cardiovascular biology remains elusive.Here we investigated whether Miat regulates cardiac response pathological hypertrophic stimuli.Methods: Both an angiotensin II (Ang II) infusion model and a transverse aortic constriction (TAC) were used adult WT Miat-null...
Evidence suggests that mitochondrial network integrity is impaired in cardiomyocytes from failing hearts. While oxidative stress has been implicated heart failure (HF)-associated remodeling, the effect of mitochondrial-targeted antioxidants, such as mitoquinone (MitoQ), on a model HF (e.g., pressure overload) not demonstrated. Furthermore, mechanism this regulation completely understood with an emerging role for posttranscriptional via long noncoding RNAs (lncRNAs). We hypothesized MitoQ...
The effectiveness of cell-based treatments for regenerative myocardial therapy is limited by low rates cell engraftment. Y-27632 inhibits Rho-associated protein kinase (ROCK), which regulates the cytoskeletal changes associated with adhesion, and has been used to protect cultured cells during their passaging. Here, we investigated whether preconditioning cardiomyocytes, derived from human-induced pluripotent stem (hiPSC-CM), improves survival engraftment in a murine model acute infarction...
Establishing modular binders as diagnostic detection agents represents a cost- and time-efficient alternative to the commonly used that are generated one molecule at time. In contrast these conventional approaches, binder can be designed in silico from individual modules to, principle, recognize any desired linear epitope without going through selection hit-validation process, given set of preexisting, amino acid–specific modules. Designed armadillo repeat proteins (dArmRP) have been...
Text-based knowledge extraction methods for populating bases have focused on binary facts: relationships between two entities. However, in advanced domains such as health, it is often crucial to consider ternary and higher-arity relations. An example capture which drug used disease at dosage (e.g. 2.5 mg/day) kinds of patients (e.g., children vs. adults). In this work, we present an approach harvest facts from textual sources. Our method distantly supervised by seed facts, uses the...
Despite the abundance of biomedical literature and health discussions in online communities, it is often tedious to retrieve informative contents for health-centric information needs.Users can query scholarly work PubMed by keywords MeSH terms, resort Google everything else.This demo paper presents DeepLife system, overcome limitations existing search engines life science topics.DeepLife integrates large knowledge bases harnesses entity linking methods, support exploration scientific...
Abstract To overcome the laborious identification of crystallisation conditions for protein X-ray crystallography, we developed a method where examined is immobilised as guest molecule in universal host lattice. We applied crystal engineering to create generic crystalline lattice under reproducible, predefined and analysed structures target molecules different size, namely two 15-mer peptides green fluorescent (sfGFP). A fusion with an N-terminal endo-α-N-acetylgalactosaminidase (EngBF)...
Introduction: MitoView 633, a far-red fluorescent dye, exhibits the ability to accumulate within mitochondria in membrane potential-dependent manner, as described by Nernst equation. This characteristic renders it promising candidate for bioenergetics studies, particularly robust indicator of mitochondrial potential (DY m ). Despite its great potential, utility live cell imaging has not been well characterized. Methods: study seeks characterize spectral properties 633 cells and evaluate...
Abstract The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target V3-base. Challenging this view, we present V3-crown Designed Ankyrin Repeat Proteins (bnDs) matching breadth V3-base bnAbs. While most bnAbs prefusion Env, bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve focusing on highly conserved residues that are accessible...
Current efforts in the biomedical ontology community focus on establishing interoperability and data integration. In covering human diseases, one of major international standards clinical practice is International Classification for Diseases (ICD), maintained by World Health Organization (WHO). Several countryand language-specific adaptations exist which share general structure WHO version but differ certain details. This complicates exchange patient records hampers integration across...