Publications by authors named "Thomas D Clark"

Paternal diet can influence the phenotype of the next generation, yet, the dietary components inducing specific responses in the offspring are not identified. Here, we use the Nutritional Geometry Framework to determine the effects of pre-conception paternal dietary macronutrient balance on offspring metabolic and behavioral traits in mice. Ten isocaloric diets varying in the relative proportion of protein, fats, and carbohydrates are fed to male mice prior to mating.

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Obesity and mood disorders are two of the most serious health issues of modern times. These health conditions are often linked, with obesity acting both as a cause and consequence of anxiety and depression. Although sex differences in the relationship between obesity and mood disorders are observed in clinical populations, the relative influence of biology versus societal conditioning is unclear.

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Obesity and mood disorders have been linked in a positive feedback loop. However, due to the bidirectional relationship between obesity and mental health, it is not clear whether anxiety is correlated with or caused by consumption of obesogenic diets. Here, we present a meta-analysis on the effects of dietary manipulation on rodent behavior in the elevated plus maze and open field test, the most common tests of anxiety-like behavior in animal models.

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Organisms have evolved biomaterials with an extraordinary convergence of high mechanical strength, toughness, and elasticity. In contrast, synthetic materials excel in stiffness or extensibility, and a combination of the two is necessary to exceed the performance of natural biomaterials. We bridge this materials property gap through the side-chain-to-side-chain polymerization of cyclic β-peptide rings.

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This paper evaluates analytical techniques that are relevant for performing reliable quantitative analysis of peptide adsorption on surfaces. Two salient problems are addressed: determining the solution concentrations of model GG-X-GG, X5, and X10 oligopeptides (G = glycine, X = a natural amino acid), and quantitative analysis of these peptides following adsorption on surfaces. To establish a uniform methodology for measuring peptide concentrations in water across the entire GG-X-GG and X n series, three methods were assessed: UV spectroscopy of peptides having a C-terminal tyrosine, the bicinchoninic acid (BCA) protein assay, and amino acid (AA) analysis.

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We show that three designed cyclic d,l-peptides are β-helical in TFE-a solvent in which the archetypal β-helical peptide, gA, is unstructured. This result represents an advance in the field of β-helical peptide foldamers and a step toward achieving β-helical structure under a broad range of solvent conditions. We synthesized two of the three peptides examined using an improved variant of our original CBC strategy.

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The adsorption to gold surfaces in aqueous solutions has been systematically evaluated for a series of model oligopeptides. The series includes GG-X-GG "host-guest" sequences, where the central X residue is one of 19 proteinogenic amino acids, and water-soluble X5 and X10 homo-oligopeptides. Irreversible adsorption on gold of GG-X-GG peptides, which lack significant secondary structure, was quantitatively analyzed by X-ray photoelectron spectroscopy (XPS).

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Conformational changes of three cyclic β-helical peptides upon adsorption onto planar fused-quartz substrates were detected and analyzed by far-ultraviolet (UV) circular dichroism (CD) spectroscopy. In trifluoroethanol (TFE), hydrophobic peptides, Leu β and Val β, form left- and right-handed helices, respectively, and water-soluble peptide WS β forms a left-handed helix. Upon adsorption, CD spectra showed a mixture of folded and unfolded conformations for Leu β and Val β and predominantly unfolded conformations for WS β.

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Cyclic β-helical peptides have been developed as model structured biomolecules for examining peptide adsorption and conformation on surfaces. As a key prerequisite to circular-dichroism (CD) analysis of these model peptides on surfaces, their conformations and the corresponding vibrational spectra in the 1400-1800 cm⁻¹ range were analyzed by vibrational circular-dichroism (VCD) spectroscopy in solution. The two model peptides ("β Leu and β Val") were examined in chloroform, where they each fold into a homogeneous well-defined antiparallel double-stranded β-helical species, as determined previously by NMR and electronic CD spectroscopy.

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This paper examines the self-assembly of cyclic β-tripeptides using density functional theory. On the basis of literature precedents, these cyclic peptides were expected to self-assemble into cylindrical structures by stacking through backbone-backbone hydrogen bonding. Our calculations show that such stacking is energetically favorable, that the association energy per cyclic peptide decreases (becomes more favorable), and that the overall macrodipole moment of the cylindrical assembly increases with the number of stacked rings, for up to eight rings.

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Beta helices--helices formed by alternating D,L-peptides and stabilized by beta-sheet hydrogen bonding--are found naturally in only a handful of highly hydrophobic peptides. This paper explores the scope of beta-helical structure by presenting the first design and biophysical characterization of a hydrophilic D,L-peptide, 1, that forms a beta helix in methanol. The design of 1 is based on the beta-hairpin/beta helix--a new supersecondary that had been characterized previously only for hydrophobic peptides in nonpolar solvents.

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We describe the deposition and properties of self-assembled monolayers (SAMs) of methyl-terminated alkanethiols on InAs(001) surface. For these model hydrophobic films, we used water contact angle measurements to survey the preparation of alkanethiol monolayers from base-activated ethanolic solutions as a function of the solution and deposition parameters, including chain length of alkanethiols, deposition time, and solution temperature and pH. We then used X-ray photoelectron spectroscopy (XPS), ellipsometry, and electrochemistry to characterize the composition and structure of octadecanethiol (ODT) monolayers deposited on InAs under optimized conditions.

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This communication describes the design and characterization of a new peptide motif that is a hybrid of beta-hairpin and beta-helical structures. This motif was supported by CD and IR spectrocopies in nonpolar organic solvents and was confirmed by NMR spectroscopy and structure calculations using NMR-derived restraints. The beta-hairpin/beta-helical motif represents a potentially attractive new structural template for a variety of possible applications in biomolecular design, such as ligands for macromolecular targets and building blocks for new protein architectures.

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This paper describes the design and characterization of a small, membraneless redox fuel cell. The smallest channel dimensions of the cell were 2 mm x 50 mum or x 200 mum; the cell was fabricated in poly(dimethylsiloxane) using soft lithography. This all-vanadium fuel cell took advantage of laminar flow to obviate the need for a membrane to separate the solutions of oxidizing and reducing components.

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This article presents a strategy for the fabrication of ordered microstructures using concepts of design inspired by molecular self-assembly and template-directed synthesis. The self-assembling components are 4-microm-thick hexagonal metal plates having sides 10 microm in length ("hexagons"), and each template consists of a 4-microm-thick circular metal plate surrounding a central cavity, the perimeter of which is complementary in shape to the external edges of a two-dimensional, close-packed array of hexagons. The hexagons and templates (collectively, "pieces") were fabricated via standard procedures and patterned into hydrophobic and hydrophilic regions using self-assembled monolayers (SAMs).

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This communication describes the fabrication of three-dimensional structures of organic polymers using principles of design inspired by protein folding. The structures consist of rigid polyhedral components with dimensions of a few millimeters ("microdomains"), representing alpha-helical and beta-sheet secondary structures, connected with flexible linkers representing loops or turns. These structures were fabricated from polyurethane using photolithographic and soft lithographic techniques.

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Hollow tubular structures of molecular dimensions perform diverse biological functions in nature. Examples include scaffolding and packaging roles played by cytoskeletal microtubules and viral coat proteins, respectively, as well as the chemical transport and screening activities of membrane channels. In the preparation of such tubular assemblies, biological systems make extensive use of self-assembling and self-organizing strategies.

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The new photochromic supramolecular system 1 is based on the E→Z isomerization of an azobenzene substituted with cyclic peptides with alternating D- and L-α-amino acids. This system allows reversible switching between inter- and intramolecularly assembled cylindrical β-sheet structures in solution as well as in thin films at the air-water interface. Moreover, the system displays the rarely observed quantitative photoinduced E→Z isomerization.

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