A quantum chemical investigation of the metal centres in cytochrome c oxidase

Quantum effects are often of key importance for the function of biological systems at molecular level. Cellular respiration, where energy is extracted from the reduction of molecular oxygen to water, is no exception. In this work, the end station of the electron transport chain in mitochondria, cytochrome c oxidase, is investigated using quantum chemical methodology. Cytochrome c oxidase contains two haems, haem a and haem a3. Haem a3, with its copper companion, CuB, is involved in the final reduction of oxygen into water. This binuclear centre receives the necessary electrons from haem a. Haem a, in turn, receives its electrons from a copper ion pair in the vicinity, called CuA. Density functional theory (DFT) has been used to clarify the charge and spin distributions of haem a, as well as changes in these during redox activity. Upon reduction, the added electron is shown to be evenly distributed over the entire haem structure, important for the accommodation of the prosthetic group within the protein. At the same time, the spin distribution of the open-shell oxidised state is more localised to the central iron. The exact spin density distribution has been disputed in the literature, however, different experiments indicating different distributions of the unpaired electron. The apparent contradiction is shown to be due to the false assumption of a unit amount of unpaired electron density; in fact, the oxidised state has about 1.3 unpaired electrons. The validity of the DFT results have been corroborated by wave function based coupled cluster calculations. Point charges, for use in classical force field based simulations, have been parameterised for the four metal centres, using a newly developed methodology. In the procedure, the subsystem for which point charges are to be obtained, is surrounded by an outer region, with the purpose of stabilising the inner region, both electronically and structurally. Finally, the possibility of vibrational promotion of the electron transfer step between haem a and a3 has been investigated. Calculating the full vibrational spectra, at DFT level, of a combined model of the two haems, revealed several normal modes that do shift electron density between the haems. The magnitude of the shift was found to be moderate, at most. The proposed mechanism could have an assisting role in the electron transfer, which still seems to be dominated by electron tunnelling.

Conformation And C-N Rotational Barrier Of Dithiocarbamate Esters Nmr And Molecular-Orbital Studies

The variable temperature proton and ambient temperature carbon-13 NMR spectra of S-methyl dithiocarbamate esters have been recorded. The results of the theoretical energy calculations (CNDO/2 and EHT types) together with the experimental data have been interpreted in terms of the molecular conformations. The barrier heights for the rotation about the thioamide C—N bond are calculated using the CNDO/2 method and the results are discussed in terms of the computed charge densities and bond orders.

Genetic control of flowering in spotted gum, Corymbia citriodora subsp. variegata and C. maculata

Genetically controlled asynchrony in anthesis is an effective barrier to gene flow between planted and native forests. We investigated the degree of genetically controlled variation in the timing of key floral developmental stages in a major plantation species in subtropical Australia, Corymbia citriodora subsp. variegata K.D. Hill and L.A.S Johnson, and its relative C. maculata K.D. Hill and L.A.S. Johnson. Flowering observations were made in a common garden planting at Bonalbo in northern New South Wales in spring on 1855 trees from eight regions over three consecutive years, and monthly on a subset of 208 trees for 12 months. Peak anthesis time was stable over years and observations from translocated trees tended to be congruent with the observations in native stands, suggesting strong genetic control of anthesis time. A cluster of early flowering provenances was identified from the north-east of the Great Dividing Range. The recognition of a distinct flowering race from this region accorded well with earlier evidence of adaptive differentiation of populations from this region and geographically-structured genetic groupings in C. citriodora subsp. variegata. The early flowering northern race was more fecund, probably associated with its disease tolerance and greater vigour. Bud abundance fluctuated extensively at the regional level across 3 years suggesting bud abundance was more environmentally labile than timing of anthesis. Overall the level of flowering in the planted stand (age 12 years) was low (8–12% of assessed trees with open flowers), and was far lower than in nearby native stands. Low levels of flowering and asynchrony in peak anthesis between flowering races of C. citriodora subsp. variegata may partially mitigate a high likelihood of gene flow where the northern race is planted in the south of the species range neighbouring native stands

Raphael Lemkin collection undated, 1763, 1915-1919, [c.1921], 1933, 1941-1952, 1983, 1989.

Lemkin is the individual primarily responsible for adoption of the United Nations Convention for the Prevention and Punishment of Genocide. The collection is arranged according to the following subject areas: personal material, material on the Genocide Convention, material on genocide.

Bernard C. Ehrenreich papers undated, 1871-1971

Primarily correspondence, scrap-books, etc. relating to activities as rabbi in Montgomery, Alabama and Stockton, California. Includes also extensive correspondence from Jewish servicemen in World War I and II, Intercollegiate Menorah Association, Zeta Beta Tau Fraternity and Camp Kawaga and letters from Stephen S. Wise, Mordecai M. Kaplan and Leon J. Obermayer. Contains also collection of picture postal cards and original minute-book of the Central Bureau of the Federation of American Zionists of Greater New York.

Protection Conferred by Infectious Coryza Vaccines Against Emergent Avibacterium paragallinarum Serovar C-1

Infectious coryza is an upper respiratory disease of chickens caused by Avibacterium paragallinarum. Outbreaks of infectious coryza caused by Av. paragallinarum serovar C-1 isolates in coryza-vaccinated flocks in Ecuador and Mexico have been reported. In the current study, the protection conferred by four commercially available, trivalent infectious coryza vaccines in chickens challenged with a serovar C-1 isolate from an apparent coryza vaccine failure in a layer flock in Mexico was evaluated. Only one infectious coryza vaccine provided a good protection level (83%) in vaccinated chickens. These results might explain the infectious coryza outbreaks in vaccinated flocks that have been observed in the field.

Induced carotenoid accumulation in Dunaliella salina and Tetraselmis suecica by plant hormones and UV-C radiation

Carotenoids prevent different degenerative diseases and improve human health. Microalgae are commercially exploited for carotenoids, including astaxanthin and β-carotene. Two commercially important microalgae, Dunaliella salina and Tetraselmis suecica, were treated with plant hormones salicylic acid (SA) and methyl jasmonate (MJ), or by UV-C radiation (T. suecica only) and a combination thereof. Significant increases in total carotenoids were found for D. salina and T. suecica after treatment with MJ (10 μmol/L) and SA (70–250 μmol/L), respectively. T. suecica also had significant increases in total carotenoids following UV-C radiation compared to control cultures. Among the carotenoids, lutein was the highest induced carotenoid. A combination of these two treatments also showed a significant increase in total carotenoids and lutein for T. suecica, when compared to controls. Plant hormones and UV-C radiation may be useful tools for increasing carotenoid accumulation in green microalgae although the responses are species- and dose-specific and should be trialed in medium to large scale to explore commercial production.

Cross Talk between Receptor Guanylyl Cyclase C and c-src Tyrosine Kinase Regulates Colon Cancer Cell Cytostasis

Increased activation of c-src seen in colorectal cancer is an indicator of a poor clinical prognosis, suggesting that identification of downstream effectors of c-src may lead to new avenues of therapy. Guanylyl cyclase C (GC-C) is a receptor for the gastrointestinal hormones guanylin and uroguanylin and the bacterial heat-stable enterotoxin. Though activation of GC-C by its ligands elevates intracellular cyclic GMP (cGMP) levels and inhibits cell proliferation, its persistent expression in colorectal carcinomas and occult metastases makes it a marker for malignancy. We show here that GC-C is a substrate for inhibitory phosphorylation by c-src, resulting in reduced ligand-mediated cGMP production. Consequently, active c-src in colonic cells can overcome GC-C-mediated control of the cell cycle. Furthermore, docking of the c-src SH2 domain to phosphorylated GC-C results in colocalization and further activation of c-src. We therefore propose a novel feed-forward mechanism of activation of c-src that is induced by cross talk between a receptor GC and a tyrosine kinase. Our findings have important implications in understanding the molecular mechanisms involved in the progression and treatment of colorectal cancer.

Role of heme in the synthesis of cytochrome c oxidase in Neurospora crassa

The role of heme in the synthesis of cytochrome c oxidase has been investigated in the mold Neurospora crassa. Iron-deficient cultures of the mold have low levels of cytochrome oxidase and delta-aminolevulinate dehydratase, the latter being the rate-limiting enzyme of the heme-biosynthetic pathway in this organism. Addition of iron to the iron-deficient cultures results in an immediate increase in the levels of delta-aminolevulinate dehydratase followed by an increase in the rate of heme synthesis and cytochrome oxidase levels. The rate of precursor labeling of the mitochondrial subunits of cytochrome oxidase is decreased preferentially under conditions of iron deficiency and addition of iron corrects this picture. Exogenous hemin addition which prevents iron-mediated induction of delta-aminolevulinate dehydratase also inhibits the increase in the activity of cytochrome oxidase and the enhanced precursor labeling of the mitochondrial subunits of cytochrome oxidase. Protein synthesis on mitoribosomes measured in vivo and in vitro is decreased under conditions of heme deficiency. Hemin addition in vitro to mitochondrial lysates prepared from heme-deficient mycelia restores a near normal rate of protein synthesis. It is concluded that heme is required for the optimal rate of translation on mitoribosomes.

J.D.C. settlements in Kherson region

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Construction of a cDNA clone for a nuclear-coded subunit of cytochrome c oxidase from rat liver

A cDNA library for 6S–9S poly(A)-containing RNA from rat liver was constructed in Image . Initial screening of the clones was carried out using single stranded 32P-labeled cDNA prepared against poly(A)-containing RNA isolated from immunoadsorbed polyribosomes enriched for the nuclear-coded subunit messenger RNAs of cytochrome c oxidase. One of the clones, pCO89, was found to hybridize with the messenger RNA for subunit VIC. The DNA sequence of the insert in pCO89 was carried out and it has got extensive homology with the C-terminal 33 amino acids of subunit VIC from beef heart cytochrome c oxidase. In addition, the insert contained 146 bp, corresponding to a portion of the 3′-non-coding region. Northern blot analysis of rat liver RNA with the nick-translated insert of pCO89 revealed that the messenger RNA for subunit VI would contain around 510 bases.

Godovoe razpredelenie osadkov (izogiety) v Krymu v 1925-1926 c.kh. g.

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C.G. Simonis Collection 1873

Letter by Simonis from 1873