A5085122609- Growth Hormone and Insulin-like Growth Factors
- Metabolism, Diabetes, and Cancer
- Genomics and Phylogenetic Studies
- Microbial Community Ecology and Physiology
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Receptor Mechanisms and Signaling
- SARS-CoV-2 detection and testing
- Gut microbiota and health
- Legume Nitrogen Fixing Symbiosis
- Fungal and yeast genetics research
- Environmental DNA in Biodiversity Studies
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Identification and Quantification in Food
- Water Treatment and Disinfection
- Protein purification and stability
- Viral Infectious Diseases and Gene Expression in Insects
- COVID-19 epidemiological studies
- Protein Structure and Dynamics
- Helicobacter pylori-related gastroenterology studies
- COVID-19 diagnosis using AI
Novo Nordisk (Denmark)
2002-2022
Aalborg University
2018-2022
Genomics (United Kingdom)
2018-2019
San Francisco State University
2010
University of California, Los Angeles
1996
University of California System
1995
New lineages of SARS-CoV-2 are potential concern due to higher transmissibility, risk severe outcomes, and/or escape from neutralizing antibodies. Lineage B.1.1.7 (the Alpha variant) became dominant in early 2021, but the association between transmissibility and factors, such as age primary case viral load remains poorly understood. Here, we used comprehensive administrative data Denmark, comprising full population (January 11 February 7, 2021), estimate household transmissibility. This...
Insulin regulates glucose homeostasis via binding and activation of the insulin receptor dimer at two distinct pairs sites 1 2. Here, we present cryo-EM studies full-length human (hIR) in an active state obtained non-saturating, physiologically relevant conditions. binds asymmetrically to under these conditions, occupying up three four possible sites. Deletion analysis together with site specific peptides analogs used show that both 2 are required for high affinity. We identify a homotypic...
Abstract. Serum concentrations of insulin‐like growth factors 1 and 2 (IGF‐1 IGF‐2), the low molecular weight form IGF binding protein (IGFBP‐1), insulin, C‐peptide GH were determined in six healthy subjects four patients with deficiency during 30 min moderate physical exercise on cycle ergometer. The load corresponded to 60% individual maximal oxygen uptake. IGF‐1 IGF‐2 by radioimmunoassays developed antibodies isolated from immunized hens egg‐yolk after separation automated acid gel...
Coarse-grained computational models of two therapeutic monoclonal antibodies are constructed to understand the effect domain-level charge-charge electrostatics on self-association phenomena at high protein concentrations. The coarse-grained representations individual using an elastic network normal-mode analysis. Two different for each antibody a compact Y-shaped and extended configuration. resulting simulations these that interact through screened done six It is observed particular...
In recent years, 16S rRNA gene amplicon sequencing has been widely adopted for analyzing the microbial communities in drinking water. However, no comprehensive attempts have made to illuminate inherent method biases specifically relating water communities. this study, we investigated impact of DNA extraction and primer choice on observed community, furthermore estimated detection limit these experimental settings. Of two kits investigated, PowerWater Isolation Kit resulted higher yield,...
Abstract Background In early 2021, the SARS-CoV-2 lineage B.1.1.7 (Alpha variant) became dominant across large parts of world. Denmark, comprehensive and real-time test, contact-tracing, sequencing efforts were applied to sustain epidemic control. Here, we use these data investigate transmissibility, introduction, onward transmission in Denmark. Methods We analyzed a set 60,178 genomes generated from high-throughput by Danish COVID-19 Genome Consortium, representing 34% all positive cases...
We used phage display to generate surrogate peptides that define the hotspots involved in protein-protein interaction between insulin and receptor. All of competed for binding had affinity constants high nanomolar low micromolar range. Based on competition studies, were grouped into non-overlapping Sites 1, 2, or 3. Some Site 1 able activate tyrosine kinase activity receptor act as agonists insulin-dependent fat cell assay, suggesting marks hotspot insulin-induced activation On other hand, 2...
We report the crystal structure of two variants Drosophila melanogaster insulin-like peptide 5 (DILP5) at a resolution 1.85 Å. DILP5 shares basic fold insulin family (T conformation) but with disordered B-chain C terminus. dimerizes in and solution. The dimer interface is not similar to that observed vertebrates, i.e. through an anti-parallel β-sheet involving termini but, contrast, formed N termini. binds activates human receptor lowers blood glucose rats. It also trehalose levels...
Insulin is thought to elicit its effects by crosslinking the two extracellular alpha-subunits of receptor, thereby inducing a conformational change in which activates intracellular tyrosine kinase signaling cascade. Previously we identified series peptides binding discrete hotspots on insulin receptor. Here show that covalent linkage such into homodimers or heterodimers results agonists antagonists, depending how are linked. An optimized agonist has been shown, both vitro and vivo, have...
Alanine scan of insulin receptor (IR)-B exon 11 and site-directed mutagenesis amino acid 718 in human IR-A IR-B were performed. Ligand affinities to wild type mutated receptors studied by displacement radioactive binding assay on secreted soluble midi or solubilized semi-purified full length stably expressed Baby Hamster Kidney cells. Phosphorylation IR response insulin, IGF1 IGF2 was measured using ELISA.Insulin, detemir glargine maximally showed two fold differences affinity for IR-B, but...
Abstract The origin of the eukaryotic cell is a major open question in biology. Asgard archaea are closest known prokaryotic relatives eukaryotes, and their genomes encode various signature proteins, indicating some elements cellular complexity prior to emergence first cell. Yet, microscopic evidence demonstrate structure uncultivated environment thus far lacking. We used primer-free sequencing retrieve 715 almost full-length Loki- Heimdallarchaeota 16S rRNA sequences designed novel...
Objectives: Research evidence suggests that chronic pouchitis is associated with intestinal dysbiosis. Faecal microbiota transplantation (FMT) has been proposed as a possible treatment. We performed 6-month prospective, open-label, single-centre cohort pilot-study (NCT03538366) to investigate if FMT could improve clinical outcome and alter gut in patients pouchitis.Materials methods: Nine adult were included allocated 14 days by enemas from five faecal donors, follow-up. Pouchitis severity...
Several studies have shown that adiponectin can lower blood glucose in diabetic mice. The aim of this study was to establish an effective production process and evaluate the anti-diabetic potential different forms mice sand rats.Human high molecular weight, mouse low weight plus human globular were expressed purified from mammalian cells or yeast. protein administered at 10-30 mg/kg i.p. b.i.d. db/db for 2 weeks. Furthermore, batches 5-15 rats 12 days.Surprisingly, none our had any effect on...
We have previously shown that a minimized insulin receptor (IR) consisting of the first 468 amino acids fused to 16 from C terminus α-subunit (CT domain) bound with nanomolar affinity (Kristensen, C., Wiberg, F. Schäffer, L., and Andersen, A. S. (1998) <i>J. Biol. Chem.</i> 273, 17780–17786). In present study, we show smaller construct has 308 residues CT domain also binds insulin. Insulin fragments or did not bind However, when these were mixed synthetic peptide corresponding domain,...
The insulin receptor (IR) is a dimeric receptor, and its activation thought to involve cross-linking between monomers initiated by binding of single molecule separate epitopes on each monomer. We have previously shown that minimized consisting the first three domains human IR fused 16 amino acids from C-terminal α-subunit was monomeric bound with nanomolar affinity (Kristensen, C., Wiberg, F. Schäffer, L., Andersen, A. S. (1998) J. Biol. Chem. 273, 17780–17786). To investigate properties...
Filamentous bacteria isolated from surface-sterilized nodules of Casuarina equisetifolia trees in México were capable reducing acetylene, a diagnostic test for nitrogenase, but unable to nodulate their host. Analysis partial 16S rRNA gene sequences suggests that the Mexican isolates are not Frankia strains members novel clade.
Through binding to and signaling via the insulin receptor (IR), is involved in multiple effects on growth metabolism. The current model for insulin−IR process one of a biphasic reaction. It thought that peptide possesses two interfaces (sites 1 2), which allow it bridge α-subunits during sequential order events involving sites 2, as well molecular interactions corresponding fast slow events, still unknown. In this study we examined series occur with help three analogues: insulin, an analogue...
Abstract In early 2021, the SARS-CoV-2 lineage B.1.1.7 became dominant across large parts of world. Denmark, comprehensive and real-time test, contact-tracing, sequencing efforts were applied to sustain epidemic control. Here, we use these data investigate transmissibility, introduction, onward transmission in Denmark. a period with stable restrictions, estimated an increased transmissibility 58% (95% CI: [56%,60%]) relative other lineages. Epidemiological phylogenetic analyses revealed that...
Translation across species of immunoassay results is often challenging due to the lack cross-species reactivity antibodies. In order investigate biology insulin and IGF1 receptors, we generated new versatile monoclonal assay antibodies using extracellular domain insulin/IGF1 hybrid receptor as bait protein in Adimab yeast antibody discovery platform antigen a rabbit platform. The resulting clones were screened for specificity well both tissue cell line derived samples. Using these...