Competitive exclusion among self-replicating molecules curtails the tendency of chemistry to diversify.

The transition of chemistry into biology is poorly understood. Key questions include how the inherently divergent nature of chemical reactions can be curtailed, and whether Darwinian principles from biology extend to chemistry. Addressing both questions simultaneously, we now show that the evolutionary principle of competitive exclusion, which states that a single niche can be stably occupied by only one species, also applies to self-replicating chemical systems, and that this principle diminishes the tendency of chemistry to diversify.

Generalist versus Specialist Self-Replicators.

Darwinian evolution, including the selection of the fittest species under given environmental conditions, is a major milestone in the development of synthetic living systems. In this regard, generalist or specialist behavior (the ability to replicate in a broader or narrower, more specific food environment) are of importance. Here we demonstrate generalist and specialist behavior in dynamic combinatorial libraries composed of a peptide-based and an oligo(ethylene glycol) based building block.

Stochastic Emergence of Two Distinct Self-Replicators from a Dynamic Combinatorial Library.

Unraveling how chemistry can give rise to biology is one of the greatest challenges of contemporary science. Achieving life-like properties in chemical systems is therefore a popular topic of research. Synthetic chemical systems are usually deterministic: the outcome is determined by the experimental conditions.

Chemical Fueling Enables Molecular Complexification of Self-Replicators*.

Unravelling how the complexity of living systems can (have) emerge(d) from simple chemical reactions is one of the grand challenges in contemporary science. Evolving systems of self-replicating molecules may hold the key to this question. Here we show that, when a system of replicators is subjected to a regime where replication competes with replicator destruction, simple and fast replicators can give way to more complex and slower ones.

Spontaneous Emergence of Self-Replicating Molecules Containing Nucleobases and Amino Acids.

The conditions that led to the formation of the first organisms and the ways that life originates from a lifeless chemical soup are poorly understood. The recent hypothesis of "RNA-peptide coevolution" suggests that the current close relationship between amino acids and nucleobases may well have extended to the origin of life. We now show how the interplay between these compound classes can give rise to new self-replicating molecules using a dynamic combinatorial approach.

Effector-Triggered Self-Replication in Coupled Subsystems.

In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication.

Redox Control over Acyl Hydrazone Photoswitches.

Photoisomerization provides a clean and efficient way of reversibly altering physical properties of chemical systems and injecting energy into them. These effects have been applied in development of systems such as photoresponsive materials, molecular motors, and photoactivated drugs. Typically, switching from more to less stable isomer(s) is performed by irradiation with UV or visible light, while the reverse process proceeds thermally or by irradiation using another wavelength.

Structural and Spectroscopic Properties of Assemblies of Self-Replicating Peptide Macrocycles.

Self-replication at the molecular level is often seen as essential to the early origins of life. Recently a mechanism of self-replication has been discovered in which replicator self-assembly drives the process. We have studied one of the examples of such self-assembling self-replicating molecules to a high level of structural detail using a combination of computational and spectroscopic techniques.

Two-dimensional soft supramolecular networks.

Two flexible multivalent molecular units are employed to self-assemble highly regular supramolecular porous networks at the solid/liquid interface. Scanning tunnelling microscopy imaging corroborated with molecular dynamics simulations make it possible to elucidate the conformational freedom behind the binding motif, which identify the architecture as a highly regular soft network.

Ultra-strong coupling of molecular materials: spectroscopy and dynamics.

We report here a study of light-matter strong coupling involving three molecules with very different photo-physical properties. In particular we analyze their emission properties and show that the excitation spectra are very different from the static absorption of the coupled systems. Furthermore we report the emission quantum yields and excited state lifetimes, which are self-consistent.

Self-assembly of a highly organized, hexameric supramolecular architecture: formation, structure and properties.

Two derivatives, (3)L and (9)L, of a ditopic, multiply hydrogen-bonding molecule, known for more than a decade, have been found, in the solid state as well as in solvents of low polarity at room temperature, to exist not as monomers, but to undergo a remarkable self-assembly into a complex supramolecular species. The solid-state molecular structure of (3)L, determined by single-crystal X-ray crystallography, revealed that it forms a highly organized hexameric entity (3)L6 with a capsular shape, resulting from the interlocking of two sets of three monomolecular components, linked through hydrogen-bonding interactions. The complicated (1)H NMR spectra observed in o-dichlorobenzene (o-DCB) for (3)L and (9)L are consistent with the presence of a hexamer of D3 symmetry in both cases.

Red blood cells mediate the onset of thrombosis in the ferric chloride murine model.

Application of ferric chloride (FeCl(3)) to exposed blood vessels is widely used to initiate thrombosis in laboratory mice. Because the mechanisms by which FeCl(3) induces endothelial injury and subsequent thrombus formation are little understood, we used scanning electron and brightfield intravital microscopy to visualize endothelial damage and thrombus formation occurring in situ. Contrary to generally accepted belief, FeCl(3) does not result in appreciable subendothelial exposure within the time frame of thrombosis.

STM insight into hydrogen-bonded bicomponent 1D supramolecular polymers with controlled geometries at the liquid-solid interface.

Bicomponent supramolecular polymers, consisting of two alternating molecules bridged through six H-bonds, are observed by STM at the solid-liquid interface. Control of the geometry of the 1D architecture was obtained by using two different connecting molecules with different conformational rigidity, affording either linear (see picture, left) or zigzag (right) motifs.

The spectrum of Trp- mutants isolated as 5-fluoroanthranilate-resistant clones in Saccharomyces bayanus, S. mikatae and S. paradoxus.

5-Fluoroanthranilic acid (FAA)-resistant mutants were selected in homothallic diploids of three Saccharomyces species, taking care to isolate mutants of independent origin. Mutations were assigned to complementation groups by interspecific complementation with S. cerevisiae tester strains.

Array comparative genomic hybridization in patients with congenital diaphragmatic hernia: mapping of four CDH-critical regions and sequencing of candidate genes at 15q26.1-15q26.2.

Congenital diaphragmatic hernia (CDH) is a common birth defect with a high mortality and morbidity. There have been few studies that have assessed copy number changes in CDH. We present array comparative genomic hybridization data for 29 CDH patients to identify and map chromosome aberrations in this disease.

NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory.

Purpose: Sotos syndrome is a genetic disorder characterized primarily by overgrowth, developmental delay, and a characteristic facial gestalt. Defects in the NSD1 gene are present in approximately 80% of patients with Sotos syndrome. The goal of this study was to determine the incidence of NSD1 abnormalities in patients referred to a clinical laboratory for testing and to identify clinical criteria that distinguish between patients with and without NSD1 abnormalities.

Intercellular signalling within vascular cells under high D-glucose involves free radical-triggered tyrosine kinase activation.

Aims/hypothesis: Diabetes mellitus is associated with endothelial dysfunction in human arteries due to the release of superoxide anions (*O(2)(-)) that was found to occur predominantly in smooth muscle cells (SMC). This study was designed to elucidate the impact of high glucose concentration mediated radical production in SMC on EC. Pre-treatment of vascular SMC with increased D-glucose enhanced release of *O(2)(-).

Pathways database system: an integrated system for biological pathways.

Motivation: During the next phase of the Human Genome Project, research will focus on functional studies of attributing functions to genes, their regulatory elements, and other DNA sequences. To facilitate the use of genomic information in such studies, a new modeling perspective is needed to examine and study genome sequences in the context of many kinds of biological information. Pathways are the logical format for modeling and presenting such information in a manner that is familiar to biological researchers.

Free fatty acid overload attenuates Ca2+ signaling and NO production in endothelial cells.

Hyperlipidemia represents a major risk factor for development of vascular dysfunction and atherosclerosis. Although the unfortunate role of low-density lipoprotein has been clearly demonstrated, the mechanistic pathways through which triglyceride-derived free fatty acids (FFAs) contribute to vascular disorders are not completely understood. Thus, the present study was designed to elucidate the effects of FFAs on cultured endothelial cells.

Anandamide-induced mobilization of cytosolic Ca2+ in endothelial cells.

1. Experiments were designed to determine whether anandamide affects cytosolic Ca2+ concentrations in endothelial cells and, if so, whether CB1 cannabinoid receptors are involved. To this effect, human umbilical vein-derived EA.

Alterations in platelet Ca2+ signalling in diabetic patients is due to increased formation of superoxide anions and reduced nitric oxide production.

Increased aggregation of platelets might contribute to the development of vascular complication in diabetes mellitus. In this study release of superoxide anions, intracellular Ca2+ signalling and nitric oxide formation stimulated by the receptor-dependent agonist adenosine 5 '-diphosphate (ADP) and the receptor-independent stimulus thapsigargin, were compared in platelets isolated from patients with Type II (non-insulin-dependent) diabetes mellitus and healthy control subjects. Diabetes augmented intracellular Ca2+ release and Ca2+ entry to ADP by 40 and 44% (control subjects: n = 11; diabetic: n = 6), while the median effective concentration (EC50) of ADP to initiate Ca2+ signalling was similar in both groups.

Fructose 1,6-bisphosphate aldolase activity in leaves of a rice mutant selected for enhanced lysine.

Unknown proteins isolated from mutant tissues of rice (Oryza sativa L.) recovered from inhibitor selections were subsequently peptide microsequenced. Database searches putatively identified one peptide as fructose 1,6-bisphosphate aldolase (EC 4.

Export of β-1,3-glucanase from mutant rice cells rechallenged and stressed with lysine plus threonine.

Mutant rice cells (Oryza sativa L.) grown in liquid suspension cultures exported greater quantities of protein and β-glucanases than controls. These mutants were isolated from anther calli resistant to 1 mM lysine plus threonine (LT), regenerated and reestablished as cell suspension cultures from seeds.

Rice protein mutant expressed in liquid suspension cultures: chitinases, β-glucanases and other proteins.

A rice mutant with unique protein expression/ transport properties has been established as cells in liquid suspension and partially characterized. Mutants were originally recovered from anther calli grown for three cycles at inhibitory levels of lysine + threonine and one cycle of S-(2-aminoethyl)cysteine. Cell suspension cultures were started from high lysine-containing seeds regenerated from the inhibitor selections.