On the Angular Independence of Sets of Atomic Orbitals

The conditions under which a set of atomic orbitals becomes angularly independent are investigated for both atomic and molecular systems. How these results can be applied to various molecules is considered

Hybrid Bond Orbitals and Bond Strengths for Pentacovalent Bonding

A brief history of the theory of hybrid bond orbitals is pre- . sented. Bond strengths and hybrid bond orbitals are derived for pentacovalent systems having five bond directions which are related by five-, four-, or threefold axes of symmetry. In none of these cases does the maximum value of the bond strength occur for the geometry in which the central atom is coplanar with the non-axial bonds. For the system with a threefold axis of symmetry, the curve of bond strength versus bond angle is sufficiently flat over a large range of angles that the non-axial bonds are amenable to bending. Finally, the experimental implication of these results is discussed

Studying Functions of All Yeast Genes Simultaneously

A method of studying the functions of all the genes of a given species of microorganism simultaneously has been developed in experiments on Saccharomyces cerevisiae (commonly known as baker's or brewer's yeast). It is already known that many yeast genes perform functions similar to those of corresponding human genes; therefore, by facilitating understanding of yeast genes, the method may ultimately also contribute to the knowledge needed to treat some diseases in humans. Because of the complexity of the method and the highly specialized nature of the underlying knowledge, it is possible to give only a brief and sketchy summary here. The method involves the use of unique synthetic deoxyribonucleic acid (DNA) sequences that are denoted as DNA bar codes because of their utility as molecular labels. The method also involves the disruption of gene functions through deletion of genes. Saccharomyces cerevisiae is a particularly powerful experimental system in that multiple deletion strains easily can be pooled for parallel growth assays. Individual deletion strains recently have been created for 5,918 open reading frames, representing nearly all of the estimated 6,000 genetic loci of Saccharomyces cerevisiae. Tagging of each deletion strain with one or two unique 20-nucleotide sequences enables identification of genes affected by specific growth conditions, without prior knowledge of gene functions. Hybridization of bar-code DNA to oligonucleotide arrays can be used to measure the growth rate of each strain over several cell-division generations. The growth rate thus measured serves as an index of the fitness of the strain

Integrative Analysis of the Mitochondrial Proteome in Yeast

In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans

Review Article Vitamin C and the Common Cold: A Retrospective Analysis of Chalmers ' Review

In 1975 Thomas Chalmers analyzed the possible effect of vitamin C on the common cold by calculating the average difference in the duration of cold episodes in vitamin C and control groups in seven placebo-controlled studies. He found that episodes were 0.11 ± 0.24 (SE) days shorter in the vitamin C groups and concluded that there was no valid evidence to indicate that vitamin C is beneficial in the treatment of the common cold. Chalmers ' review has been extensively cited in scientific articles and monographs. However, other reviewers have concluded that vitamin C significantly alleviates the symptoms of the common cold. A careful analysis of Chalmers ' review reveals serious shortcomings. For example, Chalmers did not consider the amount of vitamin C used in the studies and included in his meta-analysis was a study in which only 0.025-0.05 g/day of vitamin C was administered to the test subjects. For some studies Chalmers used values that are inconsistent with the original published results. Using data from the same studies, we calculated that vitamin C (1-6 g/day) decreased the duration of the cold episodes by 0.93 ± 0.22 (SE) days; the relative decrease in the episode duration was 21%. The current notion that vitamin C has no effect on the common cold seems to be based in large part on a faulty review written two decades ago. Key teaching points: • In 1975 Thomas Chalmers published a meta-analysis of studies that have examined the role of vitamin C supplementation on common cold morbidity. • Chalmers ' paper is often cited as proof that vitamin C has no value in treating the common cold. • The present study shows that Chalmers ' analysis is fraught with errors and misleading data from the original studies

Verification of Proteomic Candidates by Mitochondrial Import

<p>Samples were incubated in the presence or absence of a membrane potential (MP) and of proteinase K (PK). Cases where import was accompanied by removal of the signal peptide (SP) are marked as “SP-processing” (+). Su9(1–69)DHFR and AAC serve as positive controls for a processed matrix protein and a nonprocessed inner membrane protein, respectively. The bar graphs indicate if a protein was more likely to be found in either the membrane or the matrix fractions of our proteomic data. The height of the bar corresponds to the number of samples in which a protein was identified with higher tag number—in the mitochondrial membrane or mitochondrial matrix fractions, respectively.</p

Evaluation of Proteomic Data for Protein Abundance and Mitochondrial Localization

<div><p>(A) Coverage of known mitochondrial proteins (Mref) by two MS proteome studies (this study and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020160#pbio-0020160-Sickmann1" target="_blank">Sickmann et al. [2003]</a>). We evaluated the 340 proteins of the mitochondrial reference set for which protein abundance data existed (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020160#pbio-0020160-Ghaemmaghami1" target="_blank">Ghaemmaghami et al. 2003</a>). The x-axis represents the median protein abundance of ten consecutive, equally sized bins of proteins.</p> <p>(B) Distribution and overlap of proteins identified by the two MS studies and known mitochondrial proteins. The total number of entries for each dataset is indicated in parentheses outside each circle. The number inside each circle indicates the number of proteins in each of the categories. In addition, the percentage of proteins that were localized to mitochondria by GFP tagging (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020160#pbio-0020160-Huh1" target="_blank">Huh et al. 2003</a>) is given in parentheses for each category.</p></div