The wide-ranging and complex spectrum of phenotypes reported herein broadens those previously described for Alström syndrome. These findings will aid physicians in making an early and accurate diagnosis and will help effect appropriate monitoring and treatment.

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

In particulate materials, such as emulsions and granular media, a "jammed" system results if particles are packed together so that all particles are touching their neighbours, provided the density is sufficiently high. This paper studies through experiment, theory and simulation, the forces that particles exert upon one another in such a jammed state. Confocal microscopy of a compressed polydisperse emulsion provides a direct 3D measurement of the dispersed phase morphology within the bulk of the sample. This allows the determination of the probability distribution of interdroplet forces, P(f) where f is the magnitude of the force, from local droplet deformations. In parallel, the simplest form of the Boltzmann equation for the probability of force distributions predicts P(f) to be of the form e(-f/p), where p is proportional to the mean force f for large forces. This result is in good agreement with experimental and simulated data.

Highly porous emulsion-templated materials were synthesized by polymerization of concentrated CO(2)-in-water (C/W) emulsions. The method does not use any organic solvents, in either the synthesis or purification steps, and no solvent residues are left in the materials. It was found that the emulsion stability is strongly affected both by the nature of the surfactant and by the viscosity of the aqueous continuous phase. By optimizing these parameters, it was possible to generate a highly porous, low-density polyacrylamide material with a pore volume of 5.22 cm(3)/g, an average pore diameter of 9.72 microm, and a bulk density of 0.14 g/cm(3). We have broadened the scope of this approach significantly by identifying inexpensive hydrocarbon surfactants to stabilize the C/W emulsions (e.g., Tween 40) and by developing redox initiation routes that allow the synthesis to be carried out at modest temperatures and pressures (20 degrees C, 65 bar). We have also extended the method to the polymerization of monomers such as hydroxyethyl acrylate, which suggests that it is possible to prepare a range of solvent-free biomaterials by this route.

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Results of microfocus X-ray diffraction at the ESRF are presented which provide unique evidence supporting a model for the structure of starch, much of this model having been previously derived only on the basis of circumstantial evidence. Here we present data from ∼2 μm regions within granules which have been subjected to no sample preparation and obtain oriented 2-D fiber patterns from the edge of B-type potato starch granules. This data is in good agreement with that previously calculated by Imberty/Perez for a B-type amylose fiber. The peripheral amylopectin helices are oriented in such a way they do not point to a single focus. No discontinuities (“grain boundaries”) within a granule could be found at the 10 μm level of resolution.

The conformational transitions that occur on heating solutions of globular proteins, unfolding and aggregation, were compared with the analogous transitions undergone by proteins adsorbed at interfaces. Fourier transform infrared spectrometry in solution and in the attenuated total reflection geometry revealed, for the globular proteins hen egg lysozyme and bovine serum albumen, both qualitative and quantitative differences between the transitions as they occur in bulk and adsorbed at an interface. In the bulk, unfolding is a sharp transition, followed sequentially on further heating by the relatively sharp onset of the intermolecular association associated with heat set gelation. In contrast, for adsorbed proteins, we found that both processes occur simultaneously over a wide range of temperatures. Proteins were more structurally stable adsorbed at a relatively hydrophilic, solid surface than at a liquid, hydrophobic surface; in the latter case, onset temperatures for both unfolding and intermolecular association were substantially lower than for bulk solutions.

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