Fold and flexibility: what can proteins' mechanical properties tell us about their folding nucleus?

The determination of a protein''s folding nucleus, i.e. a set of native contacts playing an important role during its folding process, remains an elusive yet essential problem in biochemistry. In this work, we investigate the mechanical properties of 70 protein structures belonging to 14 protein families presenting various folds using coarse-grain Brownian dynamics simulations. The resulting rigidity profiles combined with multiple sequence alignments show that a limited set of rigid residues, which we call the consensus nucleus, occupy conserved positions along the protein sequence. These residues'' side chains form a tight interaction network within the protein''s core, thus making our consensus nuclei potential folding nuclei. A review of experimental and theoretical literature shows that most (above 80%) of these residues were indeed identified as folding nucleus member in earlier studies.     

Transgenerational effects of the holocaust: Externalization of aggression in second generation of holocaust survivors.

Examined the psychological characteristics of the children of holocaust survivors. 38 males and females in their late 20's were interviewed; the parents of 19 Ss were holocaust survivors, and the parents of the other 19 Ss were in Israel during World War II and did not suffer directly. It was hypothesized that reactions of the children of the holocaust survivors would include guilt rather than external aggression and a tendency not to externalize aggressive impulses in reaction to frustrating events. The Ss' reactions to a projective test were analyzed, and the responses provide support for the major hypothesis. Results show that sons and daughters of holocaust survivors were less likely to externalize aggression than were those in a control group. This finding is supported by the content analysis of the structured interview conducted with the Ss in both groups. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Water absorption properties of phosphate glass fiber‐reinforced poly‐ϵ‐caprolactone composites for craniofacial bone repair

The moisture uptake of polymers and composites has increasing significance where these materials are specified for invasive, long‐term medical applications. Here we analyze mass gain and the ensuing degradation mechanisms in phosphate glass fiber reinforced poly‐?‐caprolactone laminates. Specimens were manufactured using in situ polymerization of ?‐caprolactone around a bed of phosphate glass fibers. The latter were sized with 3‐aminopropyltriethoxysilane to control the rate of modulus degradation. Fiber content was the main variable in the study, and it was found that the moisture diffusion coefficient increased significantly with increasing fiber volume fraction. Diffusion, plasticization, and leaching of constituents appear to be the dominant aspects of the process over these short‐term tests. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Infiltration and Top Seed Growth-Textured YBCO Bulks With Multiple Holes

The recently reported hole-patterned YBa₂Cu₃O _y (Y123) bulks with improved superconducting properties are highly interesting from material quality and application variety points of view. It is well known that the core of plain bulk superconductors needs to be fully oxygenated and some defects like cracks, pores, and voids must be suppressed in order that the material can trap a high magnetic field or carry a high current density. To minimize the above defects, we have used a combination of standard superconducting ceramic processing and an infiltration technique to prepare regularly perforated YBa₂Cu₃O _y (Y123) bulk superconductors. This process leads to negligible shrinkage upon annealing and a uniform distribution of Y211 inclusions. Texture was evidenced by neutron pole figure measurements. Flux mapping was used to verify the superconducting homogeneity of the samples and to investigate the field-trapping ability. In addition, the textured drilled samples were reinforced using resin or metal impregnation and the influence of the different processing steps on the hardness of the materials has been investigated.     

Synthesis of polymer materials for use as cell culture substrates

Up to today, several techniques have been used to maintain cells in culture for studying many aspects of cell biology and physiology. More often, cell culture is dependent on proper anchorage of cells to the growth surface. Thus, poly-l-lysine, fibronectin or laminin are the most commonly used substrates. In this study, electrosynthesized biocompatible polymer films are proposed as an alternative to these standard substrates. The electrosynthesized polymers tested were polyethylenimine, polypropylenimine and polypyrrole. Then, the adhesion, proliferation and morphology of rat neuronal cell lines were investigated on these polymer substrates in an attempt to develop new and efficient polymer materials for cell culture. During their growth on the polymers, the evolution of the cell morphology was monitored using both confocal microscopy and immunohistochemistry, leading to the conclusion of a normal development. An estimation of the adhesion and proliferation rates of rat neuronal cell cultures indicated that polyethylenimine and polypropylenimine were the best substrates for culturing olfactory neuronal cells. A method to favour the differentiation of the neuronal cells was also developed since the final aim of this work is to develop a biosensor for odour detection using differentiated neuronal cells as transducers. Consequently, a biosensor was microfabricated using silicon technology. This microsystem allowed us to culture the cells on a silicon wafer and to position the cells on certain parts of the silicon wafer.     

Engineering a pharmacologically superior form of leptin for the treatment of obesity

Leptin plays a central role in the homeostasis of body weight through its regulatory effects on appetite and energy expenditure, yet in trials as a therapeutic agent for the treatment of obesity in humans it has been disappointing. The poor clinical efficacy of leptin results from its short circulating half-life, low potency and poor solubility, necessitating large and frequent doses to obtain even modest clinical benefit. Engineered Fc-leptin immunofusins, consisting of the Fc fragment of an immunoglobulin gamma chain followed by leptin, exhibit improved pharmacological properties with very consistent and potent biological activities. Furthermore, in extending the circulating half-life of the protein in vivo from a few minutes for leptin to many hours for Fc-leptin, these proteins have the potential to reduce drastically the dosage and frequency of administration required to obtain clinical benefit. The results of this study show that the engineered leptin immunofusins described here have significantly enhanced pharmacological properties in comparison with the recombinant leptin that was used in clinical trials. As such, they could represent an important step towards a therapeutically superior form of leptin if the disappointing performance of leptin in early clinical trials was due to its poor pharmacological properties rather than any conceptual weakness in the strategy of using leptin for the treatment of obesity and its related disorders.