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Mental retardation MR occurs in approximately 3 of the population and therefore significantly impacts public health. Despite this relatively high prevalence, the specific causes of MR remain unknown in most cases, although both genetic and environmental factors are known to contribute. We describe a consanguineous family with autosomal recessive AR nonsyndromic MR NSMR. Because the consanguinity of this family is complex, we explore alternative approaches for generating accurate estimates of the evidence for linkage in this family, and demonstrate evidence for linkage to chromosome 19p13 lod score ranging from 1.2 to 3.5, depending on assumptions of allele frequencies. Fine mapping of the linked region defined a critical region of 3.6 Mb, which overlaps with a previously reported gene CC2D1A for MR. However, no mutations in the coding region of this gene are present in the family we describe. These results suggest that another gene causing autosomal recessive nonsyndromic MR ARNSMR is located within this genomic region. © 2008 WileyLiss, Inc.

The nitroxide-mediated polymerization of styrenic monomers containing oligo(ethylene glycol) (OEGn) moieties was chosen for the preparation of biocompatible polymer brushes tethered to silicon oxide surfaces due to the broad range of monomer structures available and the use of a nonmetallic initiator. These surfaces were characterized by near-edge X-ray absorption fine structure and water contact angle measurements. The biocompatibility of these grown polymer brushes was studied and compared with deposited assemblies of surface-bound OEGn-terminated silanes with selected chain lengths. Grown polymer brushes with short OEGn side chains suppressed protein adsorption significantly more than the deposited assemblies of short OEGn chains, and this was attributed to higher surface coverage by the brushes. Cell adhesion studies confirmed that OEGn-containing polymer brushes are particularly effective in preventing nonspecific adhesion. Studies of protein adsorption and cell localization carried out with specific ligands on surfaces patterned demonstrated the potential of these surface-tethered polymer brushes for the formation of micro- and nanoscale devices.

The chemistry and topography of a surface affect biological response and are of fundamental importance, especially when living systems encounter synthetic surfaces. Most biomolecules have immense recognition power (specific binding) and simultaneously have a tendency to physically adsorb onto a solid substrate without specific receptor recognition (nonspecific adsorption). Therefore, to create useful materials for many biotechnology applications, interfaces are required that have both enhanced specific binding and reduced nonspecific binding. Thus, in applications such as sensors, the tailoring of surface chemistry and the use of micro or nanofabrication techniques becomes an important avenue for the production of surfaces with specific binding properties and minimal background interference. Both self-assembled monolayers (SAMs) and polymer brushes have attracted considerable attention as surface-active materials. In this review, we discuss both of these materials with their potential applications in biotechnology. We also summarize lithographic methods for pattern formation using combined top-down and bottom-up approaches and briefly discuss the future of these materials by describing emerging new applications.

Monodisperse colloids have been synthesized from the acid labile polymer poly tert-butyl-methacrylate. They can be loaded with photoacid generator and crystallized into polymer opal photonic crystals. Irradiation with UV-light followed by baking and development with aqueous base allows subsequent patterning of the opaline films. This chemical approach makes it possible to use the self-assembly of this colloids (opal formation) to form a large-scale periodic structure and to introduce optical defects with UV-lithography.

Large area microdomain alignment in a ferroelectric liquid crystalline diblock copolymer (LCBCP) poly(styrene)-block-poly(isoprene-LC), (PS−PILC), incorporating a biphenyl 3-nitro-4-alkoxy-benzoate LC mesogenic group and a non-LC block hexagonally packed cylinder microstructure, was successfully accomplished by application of a magnetic field at elevated temperatures. Small- and medium-angle X-ray scattering demonstrated that the PS cylinders in the LC matrix orient over large areas with their long axes perpendicular to the applied magnetic field. Correspondingly, the smectic layers of the LC mesophase in the matrix are also perpendicular to the field as the anchoring of the mesogens at the intermaterial dividing surface (IMDS) between the cylindrical microdomains and the matrix is planar (homogeneous) in this material. A negative diamagnetic anisotropy for the LC mesogens is inferred from the data. A lamellar sample was also studied and found to exhibit no preferred microstructural orientation when subjected to the magnetic field. This result is consistent with the orientational state degeneracy of planar anchoring of mesogens at the flat lamellar IMDS and closely parallels our prior results obtained by orientation of nonferroelectric LCBCPs using oscillatory shear.

Surface-grafted styrene-based homopolymer and diblock copolymer brushes bearing semifluorinated alkyl side groups were synthesized by nitroxide-mediated controlled radical polymerization on planar silicon oxide surfaces. The polymer brushes were characterized by X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure (NEXAFS), and time-dependent water contact angle measurements. Angle-resolved XPS studies and water contact angle measurements showed that, in the case of the diblock copolymer brushes, the second block to be added was always exposed at the polymer−air interface regardless of its surface energy. Values of z*/Rg were estimated based on the radius of gyration, Rg, of the grafted homopolymer or block copolymer chains for the grafted brushes and thickness of the brush, z*. The fact that z*/Rg > 1 suggests that all these brushes are stretched. These results support the idea that after grafting the first block onto the surface the nitroxide-end capped polymer chains were able to polymerize the second block in a “living” fashion and the stretched brush so formed was dense enough that the outermost block in all cases completely covers the surface. NEXAFS analysis showed a relationship between the surface orientation of the fluorinated side chains and brush thickness with thicker brushes having more oriented side chains. Time-dependent water contact angle measurements revealed that the orientation of the side chains of the brush improved the surface stability toward reconstruction upon prolonged exposure to water.

A model system of side-group liquid crystalline polymers (SGLCPs) with systematically varied molecular weight (from 78 to 420 kg/mol; PDI ≤ 1.16) and spacer length (8−12 atoms long) was prepared by polymer analogous synthesis. Matching the structure of the mesogenic units to that of the nematic solvent produced excellent solubility, even at molecular weights an order of magnitude greater than in prior literature on SGLCP solutions. Addition of up to 10 wt % polymer did not affect the ordinary and extraordinary refractive indices of the nematic host (4-pentyl-4‘-cyanobiphenyl, 5CB), indicating that the order parameter was not significantly affected by the polymer.

A novel system for surface-initiated enzymatic polymerization of a film of polyhydroxyalkanoate (PHA) on solid surfaces has been developed and characterized. PHAs are aliphatic polyesters produced by a variety of microorganisms as a reserve of carbon and energy, and their properties range from elastomers to thermoplastics, depending on their monomeric composition. The PHA synthase from Ralstonia eutropha H16 was expressed as a poly-histidine fusion in Escherichia coli and immobilized onto several solid substrates through a transition-metal complex, Ni²⁺−nitrilotriacetic acid. The immobilized PHA synthase catalyzed the surface-initiated polymerization of 3-(R)-hydroxybutyryl-CoA, forming a polymer film with a uniform thickness on the surface. In this work, we describe the patterned immobilization of the intact enzyme on silicon and subsequent enzymatic polymerization. The immobilized enzyme had a lower specific activity and did not exhibit a lag phase as compared to the soluble enzyme.

Hydrogels have gained broad acceptance as a class of biocompatible materials. In this paper, we report the topographic patterning and regiospecific functionalization of hydrogel surfaces. Both photolithography and soft lithography are combined in a hybrid process to form these topographic features. By functionalization of a base layer surface followed by lithographic patterning steps, it is possible to introduce chemical functions to specific regions of the patterned surface. The model systems investigated were based on 2-hydroxyethyl methacrylate (HEMA), which is well-known for its low toxicity and widespread use in biomedical applications. Tests of Ni−NTA modified hydrogel surfaces showed successful binding of fluorescently labeled proteins to selected regions of the patterned hydrogel surface. These processes can be expanded to a wide range of monomer systems.

We have synthesized and characterized rod−coil diblock, triblock, and starblock copolymers of controlled molecular weight by stable free radical polymerization, where the rod part consists of “mesogen jacketed liquid crystalline segments” (MJLCP). The MJLCP segment examined in our studies is poly{2,5-(4-butylbenzoyl)oxystyrene} (PBBOS) while the coil part is poly(styrene). SAXS studies of the block copolymers at room temperature predominantly show only a first-order maximum in their SAXS spectra. Above the Tg of the two blocks (~150 °C) no phase-separated morphology could be detected in temperature-dependent SAXS measurements of the block copolymers. Slow cooling regenerates the morphology, indicating very slow ordering kinetics. The effects of variation in molecular architecture and increasing topological constraint in going from homopolymer to star block copolymer on melt rheology (i.e., viscosity, relaxation times, and activation energies) are reported. In the master curves of all the block copolymers and homopolymers studied, nonterminal behavior was observed at low shear frequencies along with the absence of an entanglement plateau. In the PBBOS homopolymer an increase in molecular weight resulted in a decrease in the modulus of the nematic phase that was associated with a greater extent of shear orientation. On varying the molecular architecture from homopolymer to diblock to starblock copolymer, a decrease in the complex viscosity was observed that is attributable to the presence of polystyrene as the second block and the effect of topological constraints on molecular relaxation. The activation energies also follow the same trend as complex viscosity and relaxation times.