Heterozygote Expression in Propionyl Coenzyme A Carboxylase Deficiency DIFFERENCES BETWEEN MAJOR COMPLEMENTATION GROUPS

A B S T R A C T We measured propionyl coenzyme A carboxylase (PCC) activity in extracts of skin fibroblasts and peripheral blood leukocytes from controls and obligate heterozygotes for PCC deficiency. 6 heterozygotes were from the pcc A complementation group; 12 were from the other major complementation group, designated pcc C. Mean PCC activity in fibroblast extracts from pcc A heterozygotes was 52% of that in controls, whereas mean PCC activity in pcc C heterozygotes was indistinguishable from that of controls. Similar results were obtained with extracts of peripheral blood leukocytes. In none of eight families (three pcc A and five pcc C) in which PCC activity was studied in both parents of an affected child were significant intrafamilial differences observed. The activities of two other mitochondrial enzymes (13-methylcrotonyl CoA carboxylase and glutamate dehydrogenase) were comparable in controls and both groups of heterozygotes. Whereas the data from pcc A heterozygotes are consistent with expected gene dosage effects, those from pcc C heterozygotes are not. Inasmuch as mammalian PCC is a large molecular weight tetramer, each protomer of which is probably composed of two nonidentical subunits, the latter results are most consistent with unbalanced rates of synthesis and(or) degradation of the two subunits in normal cells with compensatory balancing in pcc C heterozygotes

Molecular cloning and nucleotide sequence of cDNA encoding the entire precursor of rat liver medium chain acyl coenzyme A dehydrogenase.

cDNA encoding the precursor of rat liver medium chain acyl-CoA dehydrogenase (EC 1.3.99.3) was cloned and sequenced. The longest cDNA insert isolated was 1866 bases in length. This cDNA encodes the entire protein of 421-amino acids including a 25-amino acid leader peptide and a 396-amino acid mature polypeptide. The identity of the medium chain acyl-CoA dehydrogenase clone was confirmed by matching the amino acid sequence predicted from the cDNA to the NH2-terminal and nine internal tryptic peptide sequences derived from pure rat liver medium chain acyl-CoA dehydrogenase. The calculated molecular masses of the precursor medium chain acyl-CoA dehydrogenase, the mature medium chain acyl-CoA dehydrogenase, and the leader peptide are 46,600, 43,700, and 2,900 daltons, respectively. The leader peptide contains five basic amino acids and only one acidic amino acid; thus, it is positively charged, overall. Cysteine residues are unevenly distributed in the mature portion of the protein; five of six are found within the NH2-terminal half of the polypeptide. Comparison of medium chain acyl-CoA dehydrogenase sequence to other flavoproteins and enzymes which act on coenzyme A ester substrates did not lead to unambiguous identification of a possible FAD-binding site nor a coenzyme A-binding domain. The sequencing of other homologous acyl-CoA dehydrogenases will be informative in this regard

Search for Extratidal Features Around 17 Globular Clusters in the Sloan Digital Sky Survey

The dynamical evolution of a single globular cluster and also of the entire Galactic globular cluster system has been studied theoretically in detail. In particular, simulations show how the 'lost' stars are distributed in tidal tails emerging from the clusters. We investigate the distribution of Galactic globular cluster stars on the sky to identify such features like tidal tails. The Sloan Digital Sky Survey provides consistent photometry of a large part of the sky to study the projected two dimensional structure of the 17 globular clusters in its survey area. We use a color-magnitude weighted counting algorithm to map (potential) cluster member stars on the sky. We recover the already known tidal tails of Pal 5 and NGC 5466. For NGC 4147 we have found a two arm morphology. Possible indications of tidal tails are also seen around NGC 5053 and NGC 7078, supporting earlier suggestions. Moreover, we find potential tails around NGC 5904 and Pal 14. Especially for the Palomar clusters than Pal 5, deeper data are needed in order to confirm or to rule out the existence of tails. For many of the remaining clusters in our sample we observe a pronounced extratidal halo, which is particularly large for NGC 7006 and Pal 1. In some cases, the extratidal halos may be associated with the stream of the Sagittarius dwarf spheroidal galaxy (e.g.,NGC 4147, NGC 5024, NGC 5053).Comment: Accepted by A&A, 24 pages, 24 figure

The 2HWC HAWC Observatory Gamma Ray Catalog

We present the first catalog of TeV gamma-ray sources realized with the recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the most sensitive wide field-of-view TeV telescope currently in operation, with a 1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an instantaneous field of view >1.5 sr and >90% duty cycle, it continuously surveys and monitors the sky for gamma ray energies between hundreds GeV and tens of TeV. HAWC is located in Mexico at a latitude of 19 degree North and was completed in March 2015. Here, we present the 2HWC catalog, which is the result of the first source search realized with the complete HAWC detector. Realized with 507 days of data and represents the most sensitive TeV survey to date for such a large fraction of the sky. A total of 39 sources were detected, with an expected contamination of 0.5 due to background fluctuation. Out of these sources, 16 are more than one degree away from any previously reported TeV source. The source list, including the position measurement, spectrum measurement, and uncertainties, is reported. Seven of the detected sources may be associated with pulsar wind nebulae, two with supernova remnants, two with blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa

Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality

OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland. DESIGN: Prospective observational study. SETTING: Renfrew and Paisley, in the West of Scotland. SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline. MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes. RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations. CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting inor being associated withshorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers

STREGA: STRucture and Evolution of the GAlaxy - I : Survey overview and first results

STREGA (STRucture and Evolution of the GAlaxy) is a guaranteed time survey being performed at the VST (the ESO Very Large Telescope Survey Telescope) to map about 150 square degrees in the Galactic halo, in order to constrain the mechanisms of galactic formation and evolution. The survey is built as a 5 yr project, organized in two parts: a core programme to explore the surrounding regions of selected stellar systems and a second complementary part to map the southern portion of the Fornax orbit and extend the observations of the core programme. The adopted stellar tracers are mainly variable stars (RR Lyraes and long-period variables) and main-sequence turn-off stars for which observations in the g, r, i bands are obtained. We present an overview of the survey and some preliminary results for three observing runs that have been completed. For the region centred on ω Cen (37 deg^2), covering about three tidal radii, we also discuss the detected stellar density radial profile and angular distribution, leading to the identification of extratidal cluster stars. We also conclude that the cluster tidal radius is about 1.2 deg, in agreement with values in the literature based on the Wilson model.Peer reviewedFinal Accepted Versio

Properties of stellar generations in Globular Clusters and relations with global parameters

ABRIDGED) We revise the formation of Galactic GCs by adding the detailed chemical composition of their different stellar generations (from 1200 giants in 19 GCs) to their global parameters. We propose to identify as GCs those showing the Na-O anticorrelation, and we classify the GCs according to kinematics and location in the Galaxy in disk/bulge, inner, and outer halo. We find that the LF of GCs is fairly independent of their population, suggesting that it is imprinted by the formation mechanism, and only marginally affected by the ensuing evolution. We show that a large fraction of the primordial population should have been lost by the proto-GCs. The extremely low Al abundances found for the primordial population of massive GCs indicate a very fast enrichment process before the formation of the primordial population. We suggest a scenario for the formation of GCs including at least 3 main phases: i) the formation of a precursor population (likely due to the interaction of cosmological structures similar to those leading to dwarf spheroidals, but residing at smaller Rgc, with the early Galaxy or with other structures), ii) which triggers a large episode of star formation (the primordial population), and iii) the formation of the current GC, mainly within a cooling flow formed by the slow winds of a fraction of the primordial population. The precursor population is very effective in raising the metal content in massive and/or metal poor (mainly halo) clusters, while its role is minor in small and/or metal rich (mainly disk) ones. Finally, we use PCA and multivariate relations to study the phase of metal-enrichment from 1st to 2nd generation. Most of the chemical signatures of GCs may be ascribed to a few parameters, the most important being [Fe/H], mass, and age of the cluster, with the location within the Galaxy also playing some role.Comment: 24 pages (+2 pages of bibliography and 5 of Appendix), 19 figures, accepted for publication on Astronomy and Astrophysic

The influence of allogenic blood transfusion in patients having free-flap primary surgery for oral and oropharyngeal squamous cell carcinoma

The influence of perioperative blood transfusion in oral and oropharyngeal squamous cell carcinoma remains uncertain. It is believed that blood transfusion downregulates the immune system and may have an influence on cancer recurrence and survival. In all, 559 consecutive patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma between 1992 and 2002 were included in this study. Known prognostic variables along with transfusion details were obtained from head and neck cancer and blood transfusion service databases, respectively. Adjusting for relevant prognostic factors in Cox regression, the hazard ratio for patients having 3 or more transfused units relative to those not transfused was 1.52 (95% confidence interval (CI) 0.93–2.47) for disease-specific and 1.52 (95% CI 1.05–2.22) for overall mortality. Blood transfusion of 3 or more units might confer a worse prognosis in patients undergoing primary surgery for oral and oropharyngeal squamous cell carcinoma. Therefore, every effort should be made to limit the amount of blood transfused to the minimum requirement