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Biomedical subjects

Martin Nilsson

Publications and source records attributed to Martin Nilsson.

7 recordsLinked to original sources

A von Willebrand factor-binding protein from Staphylococcus lugdunensis.

In the present study, a phage display library covering the genome of Staphylococcus lugdunensis, was affinity-selected against von Willebrand factor (vWf). This led to the identification of a gene, vwbl, encoding a putative cell surface protein of 2060 amino acids, denoted vWbl. The deduced protein has an overall organisation typical of staphylococcal cell surface proteins, with an N-terminal signal peptide, and a C-terminal cell wall sorting signal. The vWf-binding part is located in repetitive domains and antibodies against vWbl or vWf can inhibit the binding. Southern blot analysis showed that vwbl was present in the 12 S. lugdunensis strains tested.

Amino Acid Sequence↗

The fibrinogen binding protein of Staphylococcus epidermidis is a target for opsonic antibodies.

Antibodies against the fibrinogen binding protein (Fbe) of Staphylococcus epidermidis significantly increased macrophage phagocytosis. Antibodies against autolysin E were opsonic but to a lesser extent. Antibodies against a novel, putatively surface-located antigen were unable to enhance phagocytosis. The severity of systemic infection of mice with S. epidermidis was reduced if the bacteria were preopsonized with anti-Fbe prior to administration. Fbe is thus a strong candidate for protein vaccination against S. epidermidis infection, and antibodies against Fbe can be used to prevent or treat infections caused by S. epidermidis.

Animals↗

Bridging nonliving and living matter.

Assembling non-biological materials (geomaterials) into a proto-organism constitutes a bridge between nonliving and living matter. In this article we present a simple step-by-step route to assemble a proto-organism. Many pictures have been proposed to describe this transition within the origins-of-life and artificial life communities, and more recently alternative pictures have been emerging from advances in nanoscience and biotechnology. The proposed proto-organism lends itself to both traditions and defines a new picture based on a simple idea: Given a set of required functionalities, minimize the physicochemical structures that support these functionalities, and make sure that all structures self-assemble and mutually enhance each other's existence. The result is the first concrete, rational design of a simple physicochemical system that integrates the key functionalities in a thermodynamically favorable manner as a lipid aggregate integrates proto-genes and a proto-metabolism. Under external pumping of free energy, the metabolic processes produce the required building blocks, and only specific gene sequences enhance the metabolic kinetics sufficiently for the whole system to survive. We propose an experimental implementation of the proto-organism with a discussion of our experimental results, together with relevant results produced by other experimental groups, and we specify what is still missing experimentally. Identifying the missing steps is just as important as providing the road map for the transition. We derive the kinetic and thermodynamic conditions of each of the proto-organism subsystems together with relevant theoretical and computational results about these subsystems. We present and discuss detailed 3D simulations of the lipid aggregation processes. From the reaction kinetics we derive analytical aggregate size distributions, and derive key properties of the metabolic efficiency and stability. Thermodynamics and kinetics of the ligation directed self-replication of the proto-genes is discussed, and we summarize the full life cycle of the proto-organism by comparing size, replication time, and energy with the biomass efficiency of contemporary unicells. Finally, we also compare our proto-organism picture with existing origins-of-life and protocell pictures. By assembling one possible bridge between nonliving and living matter we hope to provide a piece in the ancient puzzle about who we are and where we come from.

Artificial Intelligence↗

Quasispecies evolution on a fitness landscape with a fluctuating peak.

A quasispecies evolving on a fitness landscape with a single peak of fluctuating height is studied. In the approximation that back mutations can be ignored, the rate equations can be solved analytically. It is shown that the error threshold on this class of dynamic landscapes is defined by the time average of the selection pressure. In the case of a periodically fluctuating fitness peak, we also study the phase shift and response amplitude of the previously documented low-pass filter effect. The special case of a small harmonic fluctuation is treated analytically.

Biological Evolution↗

Optimal mutation rates in dynamic environments.

In this paper, we study the evolution of the mutation rate for simple organisms in dynamic environments. A model based on explicit population dynamics at the gene sequence level, with multiple fitness coding loci tracking a moving fitness peak in a random fitness background, is developed and an analytical expression for the optimal mutation rate is derived. The optimal mutation rate per genome is approximately independent of genome length, something that has been observed in nature. Furthermore, the optimal mutation rate is a function of the absolute, not relative, replication rate of the superior gene sequences. Simulations confirm the theoretical predictions.

Computer Simulation↗

A novel von Willebrand factor binding protein expressed by Staphylococcus aureus.

When a shotgun phage-display library of Staphylococcus aureus Newman was affinity selected (panned) against recombinant von Willebrand factor (vWf), a novel von Willebrand factor binding protein (vWbp) was found. Experimental data indicate that the interaction between vWbp and vWf is very specific and mediated by a region of 26 aa residues in the C-terminal part of vWbp. vWbp has an N-terminal secretory signal sequence but no cell wall anchoring motif, suggesting a soluble extracellular location. Mature vWbp could be purified from the culture supernatant and the identity of the protein was confirmed by N-terminal sequencing. vWbp migrates with an apparent molecular mass of 66 kDa and the deduced protein consists of 482 aa. The gene encoding vWbp, named vwb, was present in all S. aureus strains investigated.

Amino Acid Sequence↗

Iodotrimethylsilane-Promoted 1,4-Addition of Copper Acetylides to alpha,beta-Unsaturated Ketones and Aldehydes.

In the presence of iodotrimethylsilane (TMSI) and lithium iodide in tetrahydrofuran, the otherwise unreactive copper acetylides add to enones present as s-trans conformers to provide good yields of the silyl enol ethers of beta-acetylido carbonyl compounds. Typically good substrates are 2-cyclopentenone, 2-cyclohexenone, alpha,beta-unsaturated aldehydes, and beta-alkoxy-alpha-enones. Copper acetylide reagents prepared from CuI and an alkynyllithium give considerably higher yields than those prepared from CuBr or CuCN. Iodotrimethylsilane is by far the most efficient silane, although trimethylsilyl triflate is useful in some cases.

Journal Article↗