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Role of cluster size in catalysis: spectroscopic investigation of gamma-Al2O3-supported Ir4 and Ir6 during ethene hydrogenation.

gamma-Al(2)O(3)-supported Ir(4) and Ir(6) were prepared by decarbonylation of tetra- and hexanuclear iridium carbonyls, respectively, and compared as catalysts for ethene hydrogenation at atmospheric pressure and temperatures in the range 273-300 K. Rates of the reaction were determined along with extended X-ray absorption fine structure (EXAFS) and IR spectra characterizing the clusters in the working catalysts. EXAFS data show that the Ir(4) and Ir(6) cluster frames remained intact during catalysis. Di-sigma-bonded ethene and pi-bonded ethene on the clusters were identified by IR spectroscopy and found to compete as the principal reaction intermediates, with the former predominating at ethene partial pressures less than about 200 Torr and the latter at higher ethene partial pressures. Hydrogen on the clusters is inferred to form by dissociative adsorption of H(2); alternatively, it is provided by OH groups of the support. The rate of ethene hydrogenation on Ir(4) is typically several times greater than that on Ir(6).

Journal Article↗

Catalysis by oxide-supported clusters of iridium and rhodium: hydrogenation of ethene, propene, and toluene.

The hydrogenation reactions of ethene, propene, and toluene were used as probes of the catalytic properties of small clusters of rhodium (Rh6) and of iridium (Ir4 and Ir6) (as well as of larger aggregates of these metals) on oxide supports (gamma-Al2O3, MgO, and La2O3). The catalysts were characterized in the working state by extended X-ray absorption fine structure (EXAFS) spectroscopy, providing evidence of the cluster structures and cluster-support interactions; by infrared spectroscopy, providing evidence of hydrocarbon adsorbates and possible reaction intermediates on the clusters; and by kinetics of the hydrogenation reactions. The EXAFS data indicate that the metal clusters, while remaining intact and maintaining their bonding to the support during catalysis, underwent slight rearrangements to accommodate reactive intermediates. As the concentrations of reactive intermediates such as pi-bonded alkenes and alkyls on the clusters increased, the cluster frames swelled, and the clusters flexed away from the support. The data indicate self-inhibition of reaction by adsorbed hydrocarbons and differences between ethene hydrogenation and propene hydrogenation that may arise primarily from different adsorbate-adsorbate interactions.

Journal Article↗

Prediction of membrane protein topology utilizing multiple sequence alignments.

A technique for prediction of protein membrane topology (intra- and extracellular sidedness) has been developed. Membrane-spanning segments are first predicted using an algorithm based upon multiply aligned amino acid sequences. The compositional differences in the protein segments exposed at each side of the membrane are then investigated. The ratios are calculated for Asn, Asp, Gly, Phe, Pro, Trp, Tyr, and Val, mostly found on the extracellular side, and for Ala, Arg, Cys, and Lys, mostly occurring on the intracellular side. The consensus over these 12 residue distributions is used for sidedness prediction. The method was developed with a set of 42 protein families for which all but one were correctly predicted with the new algorithm. This represents an improvement over previous techniques. The new method, applied to a set of 12 membrane protein families different from the test set and with recently determined topologies, performed well, with 11 of 12 sidedness assignments agreeing with experimental results. The method has also been applied to several membrane protein families for which the topology has yet to be determined. An electronic prediction service is available at the E-mail address tmap@embl-heidelberg.de and on WWW via http://www.embl-heidelberg.de.

Amino Acid Sequence↗

Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A.

We have cloned and sequenced the complete complementary DNA of the oestrogen receptor (ER) present in the breast cancer cell line MCF-7. The expression of the ER cDNA in HeLa cells produces a protein that has the same relative molecular mass and binds oestradiol with the same affinity as the MCF-7 ER. There is extensive homology between the ER and the erb-A protein of the oncogenic avian erythroblastosis virus.

Amino Acid Sequence↗

Fingers and helices.

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Amino Acid Sequence↗

Observation of ligand effects during alkene hydrogenation catalysed by supported metal clusters.

Homogeneous organometallic catalysts and many enzymes activate reactants through coordination to metal atoms; that is, the reactants are turned into ligands and their reactivity controlled through other ligands in the metal's coordination sphere. In the case of supported metal clusters, catalytic performance is influenced by the support and by adsorbed reactants, intermediates or products. The adsorbates are usually treated as ligands, whereas the influence of the supports is usually ascribed to electronic interactions, even though metal clusters supported on oxides and zeolites form chemical bonds to support oxygen atoms. Here we report direct observations of the structure of supported metal clusters consisting of four iridium atoms, and the identification of hydrocarbon ligands bound to them during propene hydrogenation. We find that propene and molecular hydrogen form propylidyne and hydride ligands, respectively, whereas simultaneous exposure of the reactants to the supported iridium cluster yields ligands that are reactive intermediates during the catalytic propane-formation reaction. These intermediates weaken the bonding within the tetrahedral iridium cluster and the interactions between the cluster and the support, while replacement of the MgO support with gamma-Al2O3 boosts the catalytic activity tenfold, by affecting the bonding between the reactant-derived ligands and the cluster and therefore also the abundance of individual ligands. This interplay between the support and the reactant-derived ligands, whereby each influences the interaction of the metal cluster with the other, shows that the catalytic properties of supported metal catalysts can be tuned by careful choice of their supports.

Journal Article↗

Health Effects of Arsenic Longitudinal Study (HEALS): description of a multidisciplinary epidemiologic investigation.

Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes, including premalignant and malignant skin tumors, total mortality, pregnancy outcomes, and children's cognitive development. In this paper, we provide descriptions of the study methods including study design, study population, data collection, response rates, and exposure and outcome assessments. We also present characteristics of the study participants including the distribution of exposure and the prevalence of skin lesion at baseline recruitment. A total of 11,746 married men and women between 18 and 75 years of age participated in the study at baseline (a response rate of 98%) and completed a full questionnaire interview that included a food frequency questionnaire, with a response rate of 98%. Among the 98% of the participants who completed the clinical evaluation, over 90% provided blood samples and spot urine samples. Higher educational status, male gender, and presence of premalignant skin lesions were associated with an increased likelihood of providing blood and urine samples. Older participants were less likely to donate a blood sample. About one-third of the participants consumed water from a well with As concentration in each of three groups: >100 microg/l, 25-100 microg/l, and <25 microg/l. Average urinary As concentrations were 140 and 136 microg/l for males and females, respectively. HEALS has several unique features, including a prospective study design, comprehensive assessments of both past and future changes in As exposure at the individual level, a large repository of biological samples, and a full dose range of As exposures in the study population. HEALS is a valuable resource for examining novel research questions on the health effects of As exposure.

Adolescent↗

Analysis of penetrance and expressivity during ontogenesis supports a stochastic choice of zebrafish odorant receptors from predetermined groups of receptor genes.

Olfactory receptor neurons select a single odourant receptor gene for expression out of a large gene family. The mechanisms of this extreme selectivity are largely unknown. We have determined in detail the developmental expression dynamics of a representative subset of the zebrafish odourant receptor repertoire, using in situ hybridization analysis. We have thus generated a dataset, which allows us to test hypotheses of odourant receptor gene regulation. The receptors chosen belong to four different groups with respect to ontogenetic onset of expression (onset groups). Statistical analysis of the data supports a model in which the final choice of an individual odourant receptor gene occurs stochastically from within a group of genes sharing a deterministically defined onset of expression. Genomic mapping revealed a pronounced correlation of onset of expression with genomic neighbourhood. During a protracted juvenile developmental period individual regulatory influences seem to modify the expression of odourant receptor genes, a notable example being a transient decrease in expressivity of two odourant receptor genes.

Animals↗

Prenatal findings in chondrodysplasia punctata, tibia-metacarpal type.

Chondrodysplasia punctata, a skeletal dysplasia with craniofacial dysmorphism and joint contractures can occur with rhizomelia, mesomelia or both. The rhizomelic form is generally lethal, whereas one form of mesomelic chondrodysplasia punctata has been described that is associated with a presumably normal lifespan and intelligence. We describe a case of a fetus suspected prenatally of having rhizomelic chondrodysplasia punctata, who was subsequently diagnosed at 1.5 years of age to have the tibia-metacarpal form of chondrodysplasia punctata. The prenatal sonographic findings of second-trimester micromelic bone shortening and third-trimester proximal femoral stippling may be present in the rhizomelic form but are not specific to this condition.

Adult↗

Effect of melatonin on pulsatile release of luteinizing hormone in female lambs.

This study investigated the effect of melatonin treatment of ewe lambs on LH pulsatility in an attempt to examine the mechanism whereby melatonin advances the onset of puberty. Six ewe lambs were given intravaginal melatonin implants at 12.8 weeks of age. Another six lambs received empty implants. All lambs were serially blood sampled every 15 minutes for six hours on several occasions prior to the onset of puberty. One week after implantation LH pulse frequency and mean LH levels were higher in treated lambs than the control lambs (pulse frequency 0.13/h vs 0.03/h; mean LH levels 2.0 +/- 0.2 ng/ml vs 1.3 +/- 0.1 ng/ml; p less than 0.05). Melatonin treatment failed to alter pulse frequency after the initial increase. Puberty was advanced by 3 weeks in the treated group. In the second experiment six lambs received melatonin implants at 13 weeks of age and another six lambs served as control. In this experiment blood samples were taken intensively during the first few weeks after treatment. Results of this study show that mean plasma LH levels and LH pulse frequency were again higher during the first week after implantation. This transient increase in LH release may be part of the mechanism initiating the eventual advancement of puberty although the significance of this increase is questionable. In both experiments the LH response to estradiol injection was monitored at various times after treatment, but no effects of melatonin were found, although the magnitude of the response increased with age.

Animals↗

Successful embryo transfer following artificial insemination of superovulated fallow deer (Dama dama).

Thirty-four European fallow deer (Dama dama dama) were randomly allocated into embryo donor (n = 12) or embryo recipient (n = 22) groups. All does were treated with controlled internal drug release (CIDR) devices for 14 days. Animals in the embryo donor group were further treated with 200 I.U. pregnant mare serum gonadotrophin (PMSG) and 0.5 units ovine follicle-stimulating hormone (FSH). PMSG was administered 72 h before withdrawal of CIDR devices and FSH was given in eight 0.063 unit injections at 12-hourly intervals starting at the time of PMSG administration. All embryo donor animals were inseminated, by laparoscopy in both uterine horns, 36 h after withdrawal of CIDR devices with 25 x 10(6) fresh spermatozoa collected from Mesopotamian fallow deer (Dama dama mesopotamica). Embryos were recovered by laparotomy on Day 3 (n = 6) or Day 6 (n = 6) after withdrawal of CIDR devices and the ovarian response was determined. In total, 22 embryos were transferred into the oviduct (2-4-cell stage, n = 14) or uterine horn (morula stage, n = 8) on Day 3 or Day 6 after withdrawal of CIDR devices respectively. The overall means (+/- s.e.m.) of total follicular response and corpora lutea were 24.2 +/- 3.5 and 14.1 +/- 3.6 respectively. The mean number of large unruptured follicles was higher on Day 6 than on Day 3 (13.5 +/- 2.9 v. 6.7 +/- 1.3, P < 0.05). The overall embryo recovery rate was 45.8%. There was no difference in pregnancy rate following transfer of embryos on either Day 3 or Day 6 (7/14 v. 5/8 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A regional comparison of developing diabetes among VA patients exposed to typical and atypical antipsychotics relative to corticosteroids and proton pump inhibitors.

BACKGROUND: Metabolic changes, including weight gain and onset of diabetes, have been associated with both systemic corticosteroid use and atypical antipsychotic drugs. The purpose of this study was to quantify and compare the risk of new-onset diabetes mellitus in a Veterans Affairs population receiving antipsychotics and corticosteroids, using persons taking proton pump inhibitors as a control group. METHODS: This study included data from subjects treated within Veterans Integrated Service Network 23 who had received an outpatient prescription in fiscal years (FY) 1999 or 2000 for a corticosteroid (CS), a proton pump inhibitor (PPI), a typical antipsychotic, or an atypical antipsychotic. Patients receiving prescriptions in more than one class were not excluded. Subjects were excluded if they had a documented diagnosis of diabetes either in the previous FY year (1998) or prior to their index prescription date. RESULTS: Thirteen percent of the population had a new diagnosis for diabetes during the two-year study. Cox-regression analysis using time dependent covariates determined a significantly higher risk of developing diabetes (RR = 1.21) in users of CS relative to PPIs. Demographic variables including age, race, gender, marital status, and VA financial classification as well as a marker for schizophrenia, were also included in the model. Comparison of both typical and atypical antipsychotics to PPIs found an increased but nonsignificant risk of developing diabetes (RR = 1.18 and RR = 1.19 respectively). CONCLUSIONS: The diabetogenic risk associated with atypical antipsychotics was found to be less than that of corticosteroids when compared to controls. Periodic monitoring of blood glucose should be considered with chronic use of an agent from either class.

Adrenal Cortex Hormones↗

PM2.5 assessment in 21 European study centers of ECRHS II: Method and first winter results.

The follow-up of a cohort of adults from 29 European centers of the former European Community Respiratory Health Survey (ECRHS) I (1989-1992) will examine the long-term effects of exposure to ambient air pollution on the incidence, course, and prognosis of respiratory diseases, in particular asthma and decline in lung function. The purpose of this article is to describe the methodology and the European-wide quality control program for the collection of particles with 50% cut-off size of 2.5 microm aerodynamic diameter (PM2.5) in the ECRHS II and to present the PM2.5 results from the winter period 2000-2001. Because PM2.5 is not routinely monitored in Europe, we measured PM2.5 mass concentrations in 21 participating centers to estimate background exposure in these cities. A standardized protocol was developed using identical equipment in each center (U.S. Environmental Protection Agency Well Impactor Ninety-Six [WINS] and PQ167 from BGI, Inc.). Filters were weighed in a single central laboratory. Sampling was conducted for 7 days per month for a year. Winter mean PM2.5 mass concentrations (November 2000-February 2001) varied substantially, with Iceland reporting the lowest value (5 microg/m3) and northern Italy the highest (69 microg/m3). A standardized procedure appropriate for PM2.5 exposure assessment in a multicenter study was developed. We expect ECRHS II to have sufficient variation in exposure to assess long-term effects of air pollution in this cohort. Any bias caused by variation in the characteristics of the chosen monitoring location (e.g., proximity to traffic sources) will be addressed in later analyses. Given the homogenous spatial distribution of PM2.5, however, concentrations measured near traffic are not expected to differ substantially from those measured at urban background sites.

Air Pollutants↗

Arsenic exposure from drinking water and risk of premalignant skin lesions in Bangladesh: baseline results from the Health Effects of Arsenic Longitudinal Study.

Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions.

Adult↗

Automated protein sequence database classification. I. Integration of compositional similarity search, local similarity search, and multiple sequence alignment.

MOTIVATION: Genome sequencing projects require the periodic application of analysis tools that can classify and multiply align related protein sequence domains. Full automation of this task requires an efficient integration of similarity and alignment techniques. RESULTS: We have developed a fully automated process that classifies entire protein sequence databases, resulting in alignment of the homologous sequences. The successive steps of the procedure are based on compositional and local sequence similarity searches followed by multiple sequence alignments. Global similarities are detected from the pairwise comparison of amino acid and dipeptide compositions of each protein. After the elimination of all but one sequence from each detected cluster of closely related proteins, the remaining sequences are compiled in a suffix tree which is self-compared to detect local sequence similarities. Sets of proteins which share similar sequence segments are then weighted according to their closeness and multiply aligned using a fast hierarchical dynamic programming algorithm. Computational strategies were devised to minimize computer processing time and memory space requirements. The accuracy of the sequence classifications has been evaluated for 12 462 primary structures distributed over 341 known families. The percentage of sequences with missed or incorrect family assignments was 6.8% on the test set. This low error level is only twice that of the manually constructed PROSITE database ( 3.4% ) and is substantially better than that found for the automatically built PRODOM database ( 34.9% ). AVAILABILITY: The resulting database, called DOMO, is available through database search routine SRS at Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. CONTACT: gracy@infobiogen.fr

Algorithms↗

Automated protein sequence database classification. II. Delineation Of domain boundaries from sequence similarities.

MOTIVATION: Decomposing each protein into modular domains is a basic prerequisite to classify accurately structural units in biological molecules. Boundaries between domains are indicated by two similar amino acid sequence segments located within the same protein (repeats) or within homologous proteins at notably different distances from their respective N- or C-termini. RESULTS: We have developed an automated method that combines such positional constraints derived from various detected pairwise sequence similarities to delineate the modular organization of proteins. The procedure has been applied to a non-redundant data set of 26 990 proteins whose sequences were taken from the PIR and SWISS-PROT databanks and shared <60% sequence identity amongst pairs. The resultant clustering, delineation and multiple alignment of 24 380 sequence fragments yielded a new database of 4364 domain families. Comparison of the domain collection with that of PRODOM indicates a clear improvement in the number and size of domain families, domain boundaries and multiple sequence alignments. The accuracy and sensitivity of the method are illustrated by results obtained for ankyrin-like repeats and EGF-like modules. AVAILABILITY: The resulting database, called DOMO, is available through the database search routine SRS at Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. CONTACT: gracy@infobiogen.fr

Algorithms↗

A new interactive protein sequence alignment program and comparison of its results with widely used algorithms.

A computer program that allows interactive sequence comparison is described. It graphically displays a search matrix using residue physiochemical characteristics and multilength segmental comparisons. The user selects through a mousing device and screen pointer the sequence spans to be matched. The results of this method are compared with those of ALIGN and BESTFIT.

Algorithms↗