Fluctuating hydrogen-bond networks govern anomalous electron transfer kinetics in a blue copper protein

We combine experimental and computational methods to address the anomalous kinetics of long-range electron transfer (ET) in mutants of Pseudomonas aeruginosa azurin. ET rates and driving forces for wild type (WT) and three N47X mutants (X = L, S, and D) of Ru(2,2′-bipyridine)2 (imidazole)(His83) azurin are reported. An enhanced ET rate for the N47L mutant suggests either an increase of the donor–acceptor (DA) electronic coupling or a decrease in the reorganization energy for the reaction. The underlying atomistic features are investigated using a recently developed nonadiabatic molecular dynamics method to simulate ET in each of the azurin mutants, revealing unexpected aspects of DA electronic coupling. In particular, WT azurin and all studied mutants exhibit more DA compression during ET (>2 Å) than previously recognized. Moreover, it is found that DA compression involves an extended network of hydrogen bonds, the fluctuations of which gate the ET reaction, such that DA compression is facilitated by transiently rupturing hydrogen bonds. It is found that the N47L mutant intrinsically disrupts this hydrogen-bond network, enabling particularly facile DA compression. This work, which reveals the surprisingly fluctional nature of ET in azurin, suggests that hydrogen-bond networks can modulate the efficiency of long-range biological ET

Long-Range Proton-Coupled Electron-Transfer Reactions of Bis(imidazole) Iron Tetraphenylporphyrins Linked to Benzoates

Concerted proton–electron transfer (CPET) reactions in iron carboxytetraphenylporphyrin complexes have been investigated using both experimental and theoretical methods. Synthetic heme models abstract H+ and e– from the hydroxylamine TEMPOH or an ascorbate derivative, and the kinetics of the TEMPOH reaction indicate concerted transfer of H+ and e–. Phenylene linker domains vary the electron donor/acceptor separation by approximately 4 Å. The rate data and extensive molecular simulations show that the electronic coupling decay constant (β) depends on conformational flexibility and solvation associated with the linker domain. Our best estimate of β is 0.23 ± 0.07 Å^(–1), a value that is near the low end of the range (0.2–0.5 Å^(–1)) established for electron-transfer reactions involving related linkers. This is the first analysis of β for a CPET reaction

Fluctuating hydrogen-bond networks govern anomalous electron transfer kinetics in a blue copper protein

We combine experimental and computational methods to address the anomalous kinetics of long-range electron transfer (ET) in mutants of Pseudomonas aeruginosa azurin. ET rates and driving forces for wild type (WT) and three N47X mutants (X = L, S, and D) of Ru(2,2′-bipyridine)2 (imidazole)(His83) azurin are reported. An enhanced ET rate for the N47L mutant suggests either an increase of the donor–acceptor (DA) electronic coupling or a decrease in the reorganization energy for the reaction. The underlying atomistic features are investigated using a recently developed nonadiabatic molecular dynamics method to simulate ET in each of the azurin mutants, revealing unexpected aspects of DA electronic coupling. In particular, WT azurin and all studied mutants exhibit more DA compression during ET (>2 Å) than previously recognized. Moreover, it is found that DA compression involves an extended network of hydrogen bonds, the fluctuations of which gate the ET reaction, such that DA compression is facilitated by transiently rupturing hydrogen bonds. It is found that the N47L mutant intrinsically disrupts this hydrogen-bond network, enabling particularly facile DA compression. This work, which reveals the surprisingly fluctional nature of ET in azurin, suggests that hydrogen-bond networks can modulate the efficiency of long-range biological ET

Evolution of Disk Galaxies in the GOODS-South Field: Number Densities and Size Distribution

We examine the evolution of the sizes and number densities of disk galaxies using the high resolution images obtained by the Great Observatories Origins Deep Survey (GOODS) with the Advanced Camera for Surveys (ACS) on the Hubble Space Telescope (HST). The multiwavelength (B,V,i,z) images allow us to classify galaxies based on their rest-frame B-band morphologies out to redshift z = 1.25. In order to minimize the effect of selection biases, we confine our analysis to galaxies which occupy the region of magnitude-size plane where the survey is almost 90% complete at all redshifts. The observed size distribution is consistent with a log-normal distribution as seen for the disk galaxies in the local Universe and does not show any significant evolution over the redshift range 0.25 < z < 1.25. We find that the number densities of disk galaxies remains fairly constant over this redshift range, although a modest evolution by a factor of four may be possible within the 2-sigma uncertainties.Comment: accepted for publication in ApJL, 4 page

Promoting dental care to children using traditional and interactive media following threat appeals

In recent years, computer games have become an important part of children’s lives. Gaming is not only one of their favorite pastime activities, but games are also increasingly used by marketers in an attempt to influence children’s purchase behavior. Today, almost every food and beverage brand targeting children has an advergame on its website. Advergames are “computer games specifically created to function as advertisements to promote brands”, containing brand identifiers such as logos and brand characters (Kretchmer, 2005: 7). Games can also be powerful learning tools. Several authors (e.g., Gee, 2003; Prensky, 2001) argue that computer games can be more enjoyable, more interesting and thus more effective than traditional learning modes to increase children’s knowledge. Empirical studies that evaluated the impact of the use of games within disciplines such as mathematics, science, language, geography and computer science show positive outcomes in terms of learning effectiveness in relation to curricular objectives (e.g., Papastergiou, 2009; Rosas et al., 2003). However, these authors mainly focus on the learning ability of games rather than their persuasive impact for social marketing purposes. In the area of health education, playing computer games has often been seen with skepticism (e.g., Bale, 1994; Funk and Buchman, 1995)

Normal growth and development in mice over-expressing the CCN family member WISP3

Loss-of-function mutations in the gene WISP3 cause the autosomal recessive human skeletal disease Progressive Pseudorheumatoid Dysplasia, whereas mice with knockout mutations of Wisp3 have no phenotype. The lack of a phenotype in the Wisp3 knockout mice has constrained studies of the protein’s in vivo function. Over-expression experiments in zebrafish indicated that WISP3 may function as a BMP and Wnt signaling modulator. To determine whether these biologic activities are retained in mice, we created two strains of transgenic mice that over-express WISP3 in a broad array of tissues. Despite strong and persistent protein over-expression, the transgenic mice remained phenotypically indistinguishable from their non-transgenic littermates. Surprisingly, WISP3 contained in conditioned medium recovered from transgenic mouse primary kidney cell cultures was able to bind BMP and to inhibit BMP signaling in vitro. Factors that account for the difference between the in vitro and in vivo activities of WISP3 remain unknown. At present, the mouse remains a challenging model organism in which to explore the biologic function of WISP3

Sclerostin: Current Knowledge and Future Perspectives

In recent years study of rare human bone disorders has led to the identification of important signaling pathways that regulate bone formation. Such diseases include the bone sclerosing dysplasias sclerosteosis and van Buchem disease, which are due to deficiency of sclerostin, a protein secreted by osteocytes that inhibits bone formation by osteoblasts. The restricted expression pattern of sclerostin in the skeleton and the exclusive bone phenotype of good quality of patients with sclerosteosis and van Buchem disease provide the basis for the design of therapeutics that stimulate bone formation. We review here current knowledge of the regulation of the expression and formation of sclerostin, its mechanism of action, and its potential as a bone-building treatment for patients with osteoporosis