Engineering Chiral Induction in Centrally Functionalized -Phenylenes.

Work on foldamers, nonbiological oligomers that mimic the hierarchical structure of biomacromolecules, continues to yield new architectures of ever increasing complexity. -Phenylenes, a class of helical aromatic foldamers, are well-suited to this area because of their structural simplicity and the straightforward characterization of their folding in solution. However, control of structure requires, by definition, control over folding handedness.

Guest-Driven Control of Folding in a Crown-Ether-Functionalized -Phenylene.

A crown-ether-functionalized -phenylene tetramer has been synthesized and coassembled with monotopic and ditopic, achiral and chiral secondary ammonium ion guests. NMR spectroscopy shows that the -phenylene forms both 1:1 and 1:2 complexes with monotopic guests while remaining well-folded. Binding of an elongated ditopic guest, however, forces the -phenylene to misfold by pulling the terminal rings apart.

Fluorine Labeling of -Phenylenes to Facilitate Conformational Analysis.

H NMR spectroscopy is a powerful tool for the conformational analysis of -phenylene foldamers in solution. However, as -phenylenes are integrated into ever more complex systems, we are reaching the limits of what can be analyzed by H- and C-based NMR techniques. Here, we explore fluorine labeling of -phenylene oligomers for analysis by F NMR spectroscopy.

Biomedically Relevant Applications of Bolaamphiphiles and Bolaamphiphile-Containing Materials.

Bolaamphiphiles (BAs) are structurally segmented molecules with rich assembly characteristics and diverse physical properties. Interest in BAs as standalone active agents or as constituents of more complex therapeutic formulations has increased substantially in recent years. The preorganized amphiphilicity of BAs allows for a range of biological activities including applications that rely on multivalency.

Twist sense control in terminally functionalized -phenylenes.

Many abiotic foldamers are based on achiral repeat units but adopt chiral geometries, especially helices. In these systems, there is no inherent preference for one handedness of the fold; however, it is well-established that the point chirality of substituents can be communicated to the helix. This capability represents a basic level of control over folding that is necessary for applications in molecular recognition and in the assembly of higher-order structures.

Solvent effects on the folding of o-phenylene oligomers.

ortho-Phenylene oligomers fold into compact helical conformations in solution, and have therefore recently emerged as a class of foldamers. Previous work has shown that their folding is controlled by arene-arene stacking interactions parallel to the helical axis. Such interactions might reasonably be expected to be sensitive to solvent, but little is known of solvent effects in this system.

Thermal macular injury from a 154 mW green laser pointer.

We report a case of accidental thermal injury due to improper use of a laser pointer obtained outside of the United States. A 13-year-old received a laser pointer as a gift and looked at a reflection of the beam. The patient underwent full ophthalmologic examination with fundus photography, spectral domain optical coherence tomography, and fluorescein angiography.

Experimental optimization of the optical and electrical properties of a half-wavelength-thick organic hetero-structure in a Micro-cavity.

In the context of progress towards the organic laser diode, we experimentally investigate the optical and electrical optimization of an OLED in a vertical λ/2 microcavity. The microcavity consists of a quarter-wavelength TiO₂/SiO₂ multilayer mirror, a half-wavelength-thick OLED and a semitransparent aluminum cathode. The Alq3/DCM2 guest-host system is used as the emitting layer.

Mapping the interaction of Snf1 with TORC1 in Saccharomyces cerevisiae.

Nutrient sensing and coordination of metabolic pathways are crucial functions for all living cells, but details of the coordination under different environmental conditions remain elusive. We therefore undertook a systems biology approach to investigate the interactions between the Snf1 and the target of rapamycin complex 1 (TORC1) in Saccharomyces cerevisiae. We show that Snf1 regulates a much broader range of biological processes compared with TORC1 under both glucose- and ammonium-limited conditions.

NETGEM: Network Embedded Temporal GEnerative Model for gene expression data.

Background: Temporal analysis of gene expression data has been limited to identifying genes whose expression varies with time and/or correlation between genes that have similar temporal profiles. Often, the methods do not consider the underlying network constraints that connect the genes. It is becoming increasingly evident that interactions change substantially with time.

Unravelling evolutionary strategies of yeast for improving galactose utilization through integrated systems level analysis.

Identification of the underlying molecular mechanisms for a derived phenotype by adaptive evolution is difficult. Here, we performed a systems-level inquiry into the metabolic changes occurring in the yeast Saccharomyces cerevisiae as a result of its adaptive evolution to increase its specific growth rate on galactose and related these changes to the acquired phenotypic properties. Three evolved mutants (62A, 62B, and 62C) with higher specific growth rates and faster specific galactose uptake were isolated.

Economics of membrane occupancy and respiro-fermentation.

The simultaneous utilization of efficient respiration and inefficient fermentation even in the presence of abundant oxygen is a puzzling phenomenon commonly observed in bacteria, yeasts, and cancer cells. Despite extensive research, the biochemical basis for this phenomenon remains obscure. We hypothesize that the outcome of a competition for membrane space between glucose transporters and respiratory chain (which we refer to as economics of membrane occupancy) proteins influences respiration and fermentation.

Prospects of yeast systems biology for human health: integrating lipid, protein and energy metabolism.

The yeast Saccharomyces cerevisiae is a widely used model organism for studying cell biology, metabolism, cell cycle and signal transduction. Many regulatory pathways are conserved between this yeast and humans, and it is therefore possible to study pathways that are involved in disease development in a model organism that is easy to manipulate and that allows for detailed molecular studies. Here, we briefly review pathways involved in lipid metabolism and its regulation, the regulatory network of general metabolic regulator Snf1 (and its human homologue AMPK) and the proteostasis network with its link to stress and cell death.

Systems biology of energy homeostasis in yeast.

The yeast Saccharomyces cerevisiae attains energy homeostasis through complex regulatory events that are predominantly controlled by the Snf1 kinase. This master regulator senses the stress and energy starvation and activates the metabolic processes to produce ATP and inhibits biosynthesis. In doing so, Snf1 controls the switch between catabolism and anabolism accordingly, and regulates the cellular growth and development in coordination with other signaling pathways.

Metabolic and transcriptional response to cofactor perturbations in Escherichia coli.

Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli to lower the level of NADH and ATP, respectively. We used a global interaction network, comprising of protein interactions, transcriptional regulation, and metabolic networks, to integrate data from transcription profiles, metabolic fluxes, and the metabolite levels.

Metabolic impact of increased NADH availability in Saccharomyces cerevisiae.

Engineering the level of metabolic cofactors to manipulate metabolic flux is emerging as an attractive strategy for bioprocess applications. We present the metabolic consequences of increasing NADH in the cytosol and the mitochondria of Saccharomyces cerevisiae. In a strain that was disabled in formate metabolism, we either overexpressed the native NAD(+)-dependent formate dehydrogenase in the cytosol or directed it into the mitochondria by fusing it with the mitochondrial signal sequence encoded by the CYB2 gene.

Using regulatory information to manipulate glycerol metabolism in Saccharomyces cerevisiae.

Metabolic engineering has emerged as an attractive alternative to random mutagenesis and screening to design cell factories for industrial fermentation processes. The design of metabolic networks has been realized by gene deletions or strong overexpression of heterologous genes. There is an increasing body of evidence that indicates complete inactivation of native genes and high-level activity of heterologous enzymes may be deleterious to the cell.

Impact of yeast systems biology on industrial biotechnology.

Systems biology is yet an emerging discipline that aims to quantitatively describe and predict the functioning of a biological system. This nascent discipline relies on the recent advances in the analytical technology (such as DNA microarrays, mass spectromety, etc.) to quantify cellular characteristics (such as gene expression, protein and metabolite abundance, etc.

Metabolic impact of redox cofactor perturbations in Saccharomyces cerevisiae.

Redox cofactors play a pivotal role in coupling catabolism with anabolism and energy generation during metabolism. There exists a delicate balance in the intracellular level of these cofactors to ascertain an optimal metabolic output. Therefore, cofactors are emerging to be attractive targets to induce widespread changes in metabolism.

Impact of overexpressing NADH kinase on glucose and xylose metabolism in recombinant xylose-utilizing Saccharomyces cerevisiae.

During growth of Saccharomyces cerevisiae on glucose, the redox cofactors NADH and NADPH are predominantly involved in catabolism and biosynthesis, respectively. A deviation from the optimal level of these cofactors often results in major changes in the substrate uptake and biomass formation. However, the metabolism of xylose by recombinant S.

Feedback phase sensitivity of a semiconductor laser subject to filtered optical feedback: experiment and theory.

We investigate experimentally and theoretically the dynamics of a semiconductor laser subject to filtered optical feedback. Depending on the feedback strength we find dynamical regimes with different dependence on the feedback phase. In particular, the influence of the feedback phase on cw emission and on frequency oscillations is characterized experimentally.

Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae.

Respiratory metabolism plays an important role in energy production in the form of ATP in all aerobically growing cells. However, a limitation in respiratory capacity results in overflow metabolism, leading to the formation of byproducts, a phenomenon known as "overflow metabolism" or "the Crabtree effect." The yeast Saccharomyces cerevisiae has served as an important model organism for studying the Crabtree effect.

Frequency versus relaxation oscillations in a semiconductor laser with coherent filtered optical feedback.

We investigate the dynamics of a semiconductor laser subject to coherent delayed filtered optical feedback. A systematic bifurcation analysis reveals that this system supports two fundamentally different types of oscillations, namely relaxation oscillations and external roundtrip oscillations. Both occur stably in large domains under variation of the feedback conditions, where the feedback phase is identified as a key quantity for controlling this dynamical complexity.

Overflow metabolism in Escherichia coli during steady-state growth: transcriptional regulation and effect of the redox ratio.

Overflow metabolism in the form of aerobic acetate excretion by Escherichia coli is an important physiological characteristic of this common industrial microorganism. Although acetate formation occurs under conditions of high glucose consumption, the genetic mechanisms that trigger this phenomenon are not clearly understood. We report on the role of the NADH/NAD ratio (redox ratio) in overflow metabolism.

Increased recombinant protein production in Escherichia coli strains with overexpressed water-forming NADH oxidase and a deleted ArcA regulatory protein.

Glycolytic flux is increased and acetate production is reduced in Escherichia coli by the expression of heterologous NADH oxidase (NOX) from Streptococcus pneumoniae coupled with the deletion of the arcA gene, which encodes the ArcA regulatory protein. In this study, we examined the overproduction of a model recombinant protein in strains of E. coli expressing NOX with or without an arcA mutation.