Lipid concentrations and the use of lipid lowering drugs: evidence from a national cross sectional survey

ObjectiveTo evaluate the prevalence of the use of lipid lowering agents and its relation to blood lipid concentrations in English adults.DesignCross sectional survey.SettingEngland, 1998.ParticipantsNationally representative sample of 13 586 adults (aged ⩾16 years) living in non-institutional households.Results Mean total cholesterol concentrations were 5.47 (SE 0.02) mmol/l in men and 5.59 (0.02) mmol/l in women. Mean HDL cholesterol concentrations were 1.28 (0.01) mmol/l in men and 1.55 (0.01) mmol/l in women. Overall, of 10 569 adults who had a valid cholesterol measurement taken 7133 (67.5%; 95% confidence interval 66.5% to 68.4%) had a total cholesterol concentration ⩾5 mmol/l, 2804 (26.5%; 25.7% to 27.4%) had a ratio of total cholesterol to HDL cholesterol ⩾5 mmol/l, and 237 (2.2%; 1.9% to 2.5%) reported taking lipid lowering drugs. Of 117 participants with no history of cardiovascular disease but whose estimated 10 year risk of coronary heart disease was ⩾30% and whose total cholesterol concentration was ⩾5 mmol/l, four (3%) were taking lipid lowering drugs. Of 385 adults aged 16-75 with a history of coronary heart disease and eligible for lipid lowering treatment, 114 (30%; 25% to 34%) were taking lipid lowering drugs, of whom only 50 (44%; 35% to 53%) had a total cholesterol concentration <5 mmol/l.ConclusionsDespite the high prevalence of dyslipidaemia in English adults, the proportion of adults taking lipid lowering drugs in 1998 was only 2.2%. Rates of treatment were low among high risk patients eligible for primary prevention with lipid lowering drugs, and less than one third of patients with established cardiovascular disease received such treatment.     

Sequence requirements for splicing by the Cne PRP8 intein

The dependence of protein splicing on conserved residues of the Cne PRP8 intein was assessed by alanine scanning mutagenesis in a foreign protein context. Corroboration was obtained for the involvement of residues at the splice junctions and of the conserved threonine and histidine of motif B. Five additional residues were identified as absolutely required for splicing. Variant W151A displayed premature C-terminal cleavage, not seen with other Cne PRP8 mutants. We propose a model whereby W151 acts to prevent premature C-terminal cleavage, favoring complete splicing as opposed to two disjointed cleavage events.     

Specific modification of gastric K+-stimulated ATPase activity by thimerosal

Treatment of hog gastric microsomes with the sulfhydryl reagent, thimerosal (ethylmercurithiosalicylate), produced differential effects on the K+-ATPase and the K+-stimulated p-nitrophenylphosphatase activities. For example, exposure to 2 mM thimerosal for 3 min severely reduced the activity of K+-stimulated ATPase, while K+-p-nitrophenylphosphatase activity was enhanced 2- to 3-fold. Higher concentration of thimerosal, or longer incubation times, also led to inhibition of K+-p-nitrophenylphosphatase. The activated state of p-nitrophenylphosphatase could be sustained by a 20-fold, or greater, dilution of treated membranes, and could be reversed by reduction of membrane SH groups by exogenous thiols. Significant activation of K+-p-nitrophenylphosphatase was not produced by p-chloromercuribenzene sulfonate, p-chloromercuribenzoate or mersalyl; however, ethyl mercuric chloride had qualitatively similar activity effects as thimerosal. Kinetics of K+-p-nitrophenylphosphatase for thimerosal-treated membranes were altered as follows: V increased; Km for p-nitrophenylphosphate unchanged for Ka for K+ increased. ATP, which is a potent inhibitor of K+-p-nitrophenylphosphatase activity in native membranes (KI approximately 200 microM). These data suggest that there are multiple SH groups which differentially influence the gastric K+-stimulated ATPase activity. Defined treatments with thimerosal are interpreted as an uncoupling of the K+-stimulated phosphatase component of the enzyme (for which p-nitrophenylphosphatase is a presumed model reaction). Such differential modifications can be usefully applied to the study of partial reactions of the enzyme and their specific role in the related H+-transport reaction.     

The influence of local spring temperature variance on temperature sensitivity of spring phenology

The impact of climate warming on the advancement of plant spring phenology has been heavily investigated over the last decade and there exists great variability among plants in their phenological sensitivity to temperature. However, few studies have explicitly linked phenological sensitivity to local climate variance. Here, we set out to test the hypothesis that the strength of phenological sensitivity declines with increased local spring temperature variance, by synthesizing results across ground observations. We assemble ground‐based long‐term (20–50 years) spring phenology database (PEP725 database) and the corresponding climate dataset. We find a prevalent decline in the strength of phenological sensitivity with increasing local spring temperature variance at the species level from ground observations. It suggests that plants might be less likely to track climatic warming at locations with larger local spring temperature variance. This might be related to the possibility that the frost risk could be higher in a larger local spring temperature variance and plants adapt to avoid this risk by relying more on other cues (e.g., high chill requirements, photoperiod) for spring phenology, thus suppressing phenological responses to spring warming. This study illuminates that local spring temperature variance is an understudied source in the study of phenological sensitivity and highlight the necessity of incorporating this factor to improve the predictability of plant responses to anthropogenic climate change in future studies.     

The cDNA sequence coding for prepro-PGS (prepro-magainins) and aspects of the processing of this prepro-polypeptide

Amphibian skin is well known as a source of peptides homologous to bioactive peptides found in mammalian gut and brain. A systematic investigation of the skin secretions from Xenopus laevis revealed several peptides not derivable from known precursors. The sequence elucidation, utilizing fast atom bombardment/mass spectrometry, of two peptides, PGS and PGS Gly-10;Lys-22, is reported. These have been independently characterized and named magainins and found to have antimicrobial activity. A mixed sequence oligonucleotide probe complementary to the mRNA sequence coding for PGS was synthesized and used to screen a Xenopus skin cDNA library. A full length cDNA species encoding prepro-PGS was isolated and characterized, and its sequence is reported. The deduced precursor sequence was found to contain one copy of PGS Gly-10;Lys-22 and five copies of PGS. The proteolytic processing of this prepro-polypeptide is discussed.     

Detection and attribution of vegetation greening trend in China over the last 30 years

The reliable detection and attribution of changes in vegetation growth is a prerequisite for the development of strategies for the sustainable management of ecosystems. This is an extraordinary challenge. To our knowledge, this study is the first to comprehensively detect and attribute a greening trend in China over the last three decades. We use three different satellite‐derived Leaf Area Index (LAI) datasets for detection as well as five different process‐based ecosystem models for attribution. Rising atmospheric CO₂ concentration and nitrogen deposition are identified as the most likely causes of the greening trend in China, explaining 85% and 41% of the average growing‐season LAI trend (LAI_GS) estimated by satellite datasets (average trend of 0.0070 yr^?1, ranging from 0.0035 yr^?1 to 0.0127 yr^?1), respectively. The contribution of nitrogen deposition is more clearly seen in southern China than in the north of the country. Models disagree about the contribution of climate change alone to the trend in LAI_GS at the country scale (one model shows a significant increasing trend, whereas two others show significant decreasing trends). However, the models generally agree on the negative impacts of climate change in north China and Inner Mongolia and the positive impact in the Qinghai–Xizang plateau. Provincial forest area change tends to be significantly correlated with the trend of LAI_GS (P < 0.05), and marginally significantly (P = 0.07) correlated with the residual of LAI_GS trend, calculated as the trend observed by satellite minus that estimated by models through considering the effects of climate change, rising CO₂ concentration and nitrogen deposition, across different provinces. This result highlights the important role of China's afforestation program in explaining the spatial patterns of trend in vegetation growth.     

Evaluation of terrestrial carbon cycle models for their response to climate variability and to CO2 trends

The purpose of this study was to evaluate 10 process‐based terrestrial biosphere models that were used for the IPCC fifth Assessment Report. The simulated gross primary productivity (GPP) is compared with flux‐tower‐based estimates by Jung et al. [Journal of Geophysical Research 116 (2011) G00J07] (JU11). The net primary productivity (NPP) apparent sensitivity to climate variability and atmospheric CO₂ trends is diagnosed from each model output, using statistical functions. The temperature sensitivity is compared against ecosystem field warming experiments results. The CO₂ sensitivity of NPP is compared to the results from four Free‐Air CO₂ Enrichment (FACE) experiments. The simulated global net biome productivity (NBP) is compared with the residual land sink (RLS) of the global carbon budget from Friedlingstein et al. [Nature Geoscience 3 (2010) 811] (FR10). We found that models produce a higher GPP (133 ± 15 Pg C yr^?1) than JU11 (118 ± 6 Pg C yr^?1). In response to rising atmospheric CO₂ concentration, modeled NPP increases on average by 16% (5–20%) per 100 ppm, a slightly larger apparent sensitivity of NPP to CO₂ than that measured at the FACE experiment locations (13% per 100 ppm). Global NBP differs markedly among individual models, although the mean value of 2.0 ± 0.8 Pg C yr^?1 is remarkably close to the mean value of RLS (2.1 ± 1.2 Pg C yr^?1). The interannual variability in modeled NBP is significantly correlated with that of RLS for the period 1980–2009. Both model‐to‐model and interannual variation in model GPP is larger than that in model NBP due to the strong coupling causing a positive correlation between ecosystem respiration and GPP in the model. The average linear regression slope of global NBP vs. temperature across the 10 models is ?3.0 ± 1.5 Pg C yr^?1 °C^?1, within the uncertainty of what derived from RLS (?3.9 ± 1.1 Pg C yr^?1 °C^?1). However, 9 of 10 models overestimate the regression slope of NBP vs. precipitation, compared with the slope of the observed RLS vs. precipitation. With most models lacking processes that control GPP and NBP in addition to CO₂ and climate, the agreement between modeled and observation‐based GPP and NBP can be fortuitous. Carbon–nitrogen interactions (only separable in one model) significantly influence the simulated response of carbon cycle to temperature and atmospheric CO₂ concentration, suggesting that nutrients limitations should be included in the next generation of terrestrial biosphere models.     

ATP synthase from bovine mitochondria. The characterization and sequence analysis of two membrane-associated sub-units and of the corresponding cDNAs

ATP synthase from bovine mitochondria is a complex of 13 different polypeptides, whereas the Escherichia coli enzyme is simpler and contains eight subunits only. Two of the bovine subunits, b and d, which had not been characterized, have been isolated from the purified enzyme. Subunits with sizes corresponding to bovine subunits b and d are evident in preparations of the enzyme from mitochondria of other species. Partial protein sequences have been determined by direct methods. On the basis of some of this information, two oligonucleotide mixtures, 17 and 18 bases in length, have been synthesized and used as hybridization probes in the isolation of clones of the cognate cDNAs. The sequences of the two proteins have been deduced from their DNA sequences. Subunit b is 214 amino acid residues in length and has a free N terminus. Subunit d is 160 amino acid residues long. Its N-terminal alanine is blocked by an N-acetyl group, as demonstrated by fast atom bombardment mass spectrometry of N-terminal peptides. The sequence near the N terminus of the b subunit is made predominantly of hydrophobic residues, whereas the remainder of the protein is mainly hydrophilic. This N-terminal hydrophobic region may be folded into an alpha-helical structure spanning the lipid bilayer. In its distribution of hydrophobic residues, this protein resembles the b subunits of ATP synthase complexes in bacteria and chloroplasts. The b subunit in E. coli forms an important structural link between the extramembrane sector of the enzyme F1, and the intrinsic membrane domain, FO. It is proposed that the bovine mitochondrial subunit b serves a similar function. If this is so, the mitochondrial enzyme, as the chloroplast ATP synthase, contains equivalent subunits to all eight of those that constitute the E. coli enzyme. Subunit d has no extensive hydrophobic sequences, and is not apparently related to any subunit described in the simpler ATP synthases in bacteria and chloroplasts.     

A novel 1745-dalton pyroglutamyl peptide derived from chromogranin B is in the bovine adrenomedullary chromaffin vesicle

1. Following the recent demonstration of a glutaminyl cyclase activity localized in adrenomedullary chromaffin vesicles, an assay was developed to isolate and characterize posttranslationally modified peptides from this tissue which contain pyroglutamate. This assay consisted of spectrometric identification of peptides before and after enzymatic removal of pyroglutamyl residues. 2. Using this procedure, a pyroglutamyl peptide (BAM-1745) was isolated and sequenced and was shown to be a significant component of adrenomedullary secretory vesicles. 3. A computer search through the Swiss-Prot protein sequence database revealed a 93% identity of BAM-1745 and a fragment of human chromogranin B (Gln580-Tyr593).     

Specific modification of gastric K+-stimulated ATPase activity by thimerosal

Treatment of hog gastric microsomes with the sulfhydryl reagent, thimerosal (ethylmercurithiosalicylate), produced differential effects on the K⁺-ATPase and the K⁺-stimulated p-nitrophenylphosphatase activities. For example, exposure to 2 mM thimerosal for 3 min severely reduced the activity of K⁺-stimulated ATPase, while K⁺-p-nitrophenylphosphatase activity was enhanced 2- to 3-fold. Higher concentration of thimerosal, or longer incubation times, also led to inhibition of K⁺-p-nitrophenylphosphatase. The activated state of p-nitrophenylphosphatase could be sustained by a 20-fold, or greater, dilution of treated membranes, and could be reversed by reduction of membrane SH groups by exogenous thiols. Significant activation of K⁺-p-nitrophenylphosphatase was not produced by p-chloromercuribenzene sulfonate, p-chloromercuribenzoate or mersalyl; however, ethyl mercuric chloride had qualitatively similar activity effects as thimerosal. Kinetics of K⁺-p-nitrophenylphosphatase for thimerosal-treated membranes were altered as follows: V increased; K_m for p-nitrophenylphosphate unchanged for K_a for K⁺ increased. ATP, which is a potent inhibitor of K⁺-p-nitrophenylphosphatase activity in native membranes (K_I ≈ 200 μM). These data suggest that there are multiple SH groups which differentially influence the gastric K⁺-stimulated ATPase activity. Defined treatments with thimerosal are interpreted as an uncoupling of the K⁺-stimulated phosphatase component of the enzyme (for which p-nitrophenylphosphatase is a presumed model reaction). Such differential modifications can be usefully applied to the study of partial reactions of the enzyme and their specific role in the related H⁺-transport reaction.