bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight change and mortality: the Nord‐Trøndelag Health Study
Authors: DRØYVOLD W. B. , LUND NILSEN T. I. , LYDERSEN S. , MIDTHJELL K. , NILSSON P. M. , NILSSON J.‐Å. , HOLMEN J. 
Published: August 2010

Abstract.Objectives.  The prevalence of obesity is increasing. Overweight and obese people have increased mortality compared with normal weight people. We investigated the effect of weight change on mortality.Design.  Prospective population study.Setting.  We utilized data from two large population‐based health studies conducted in 1984–86 and 1995–97 respectively. Cox proportional hazards models were used to calculate mortality rate ratios (RRs) with 95% confidence intervals (CIs) between people with a stable weight and people who lost or gained weight.Subjects.  Totally 20 542 men and 23 712 women aged 20 years or more, without cardiovascular disease or diabetes at the first survey and without a history of cancer at the second survey were followed up on all‐cause mortality for 5 years after the second survey.Results.  We found no association between weight gain and mortality. People who lost weight had a higher total mortality rate compared with those who were weight stable [RR was 1.6 (95% CI: 1.4–1.8) in men and 1.7 (95% CI: 1.5–2.0) in women]. Similar associations were found for cardiovascular and noncardiovascular mortality. Additional analysis showed a linear increase in mortality rates across categories of weight loss for both men and women (P < 0.001). There was a statistically significant interaction between weight change and initial BMI, but only amongst men (P = 0.001).Conclusions.  Weight loss, but not weight gain, was associated with increased mortality amongst men and women. Although underlying undiagnosed disease is the most plausible explanation for this finding, the similar associations found for total mortality, cardiovascular mortality, and noncardiovascular mortality makes the causal pathway somewhat enigmatic.
Exhaled NO and iNOS expression in sputum cells of healthy, obese and OSA subjects
Authors: Depalo A. , Carpagnano G. E. , Spanevello A. , Sabato R. , Cagnazzo M. G. , Gramiccioni C. , Foschino‐Barbaro M. P. 
Published: August 2010

Abstract.Background.  Obstructive sleep apnoea (OSA) is associated with airways inflammation; a key role in this regard seems to be played by nitric oxide (NO). The aim of this study was to measure exhaled NO and expression of its enzyme, the inducible nitric oxide synthase (iNOS) in cells of induced sputum in OSA patients and in obese subjects without sleep apnoea and to correlate these inflammatory markers with severity of OSA.Methods.  We enrolled 18 obese patients with OSA (10 men, age 48.2 ± 8.4 years), 15 obese patients without OSA (eight men, age 52.8 ± 11 years) and 10 healthy subjects (five men, age 42 ± 4 years). Exhaled NO was measured using a chemiluminescence analyser; iNOS expression was measured in the sputum cells by immunocytochemistry.Results.  Exhaled NO resulted significantly increased in OSA and in obese patients (23.1 ± 2.1 and 17.9 ± 2.1 p.p.b.) than in healthy subjects (7.2 ± 0.6 p.p.b.; P < 0.001). OSA and obese patients showed a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to healthy subjects. In addition, OSA and obese patients showed higher iNOS expression in neutrophils and in macrophages with respect to healthy subjects. A positive correlation between exhaled NO, iNOS expression and AHI was observed.Conclusions.  These data confirm the presence of airway inflammation in OSA and in obese patients, and suggest the possible role for NO and iNOS expression in neutrophils of the induced sputum as noninvasive markers to identify and monitor the airway inflammation in these subjects.
T64A polymorphism in β3‐adrenergic receptor gene (ADRB3) and coronary heart disease: a case‐cohort study and meta‐analysis
Authors: Zafarmand M. H. , Van Der Schouw Y. T. , Grobbee D. E. , De Leeuw P. W. , Bots M. L. 
Published: August 2010

Abstract.Objectives.  A missense mutation of the human ADRB3 gene replacing tryptophan with arginine at codon 64 (Trp64Arg) has been related to obesity, insulin resistance, earlier onset of noninsulin‐dependent diabetes mellitus and hypertension. These findings may also suggest an increased risk of coronary heart disease (CHD). We therefore investigated the role of this polymorphism on the occurrence of acute myocardial infarction (AMI) and CHD in a population of healthy Dutch women.Design.  We performed a case‐cohort study in a prospective cohort of 15 236 initially healthy Dutch women. We applied a Cox proportional hazards model with an estimation procedure adapted for case‐cohort designs to study the relationship between the polymorphism and AMI (n = 71) and CHD (n = 211). In addition, a meta‐analysis of published studies was performed using a random effect model.Results.  Using the dominant model, carriers of the arginine allele (n = 222) compared to those with the more common genotype (n = 1508) were not at increased risk of AMI (hazard ratio = 1.60; 95% CI, 0.86–2.96) and for CHD (HR = 1.36; 95% CI, 0.92–2.02). We did not find any relationship using recessive and additive models, either. Our meta‐analysis corroborated these findings by showing no significant association between the polymorphism and risk of CHD using different genetic models.Conclusions.  Our study in combination with a meta‐analysis of previous reports do not provide support for a role of missense mutation replacing tryptophan with arginine at codon 64 (Trp64Arg) at the human ADRB3 gene in CHD risk.
Efficacy and safety of anticoagulant prophylaxis to prevent venous thromboembolism in acutely ill medical inpatients: a meta‐analysis
Authors: Själander A. , Jansson J.‐H. , Bergqvist D. , Eriksson H. , Carlberg B. , Svensson P. 
Published: August 2010

Abstract.Objectives.  Venous thromboembolism (VTE) is a potentially serious complication of hospitalization and immobilization. The use of anticoagulant prophylaxis in acutely ill medical inpatients is still under debate. New data including a recent meta‐analysis have recently been published. We aim at studying the efficacy and safety of anticoagulant prophylaxis in acutely ill medical inpatients, and demonstrate differences between meta‐analyses due to different data extraction from the heterogeneous studies included.Subjects.  The Cochrane Library, MEDLINE and EMBASE were searched from 1980 to present. Manual searches were performed regarding abstracts from major meetings. Seven blinded randomized controlled clinical trials assessing the prophylactic effect of heparin in acutely ill medical patients were identified and included in the meta‐analysis.Results.  Low‐molecular weight heparin (LMWH) prophylaxis prevented 48% of symptomatic pulmonary embolism (PE), 48% of symptomatic deep vein thrombosis (DVT) (not significant) and 51% of asymptomatic DVT. A nonsignificant trend towards higher bleeding risk during LMWH prophylaxis was found. Death was not significantly affected. We compared our data with a recent meta‐analysis with different study selection and data extraction and found similar results.Conclusions.  As DVT and PE are manifestations of the same illness, VTE, one can argue that anticoagulant prophylaxis prevents approximately half of the expected events. Most medical inpatients have short hospital stays, and a low risk of VTE. The important task for the clinician is to identify patients with a sufficiently high risk of symptomatic VTE to warrant LMWH prophylaxis. Despite differences in study selection and data extraction, our study shows results similar to a recent meta‐analysis.
SIRT6 in DNA repair, metabolism and ageing
Authors: Lombard D. B. , Schwer B. , Alt F. W. , Mostoslavsky R. 
Published: August 2010

Abstract.Ageing, or increased mortality with time, coupled with physiologic decline, is a nearly universal yet poorly understood biological phenomenon. Studies in model organisms suggest that two conserved pathways modulate longevity: DNA damage repair and Insulin/Igf1‐like signalling. In addition, homologs of yeast Sir2 – the sirtuins – regulate lifespan in diverse organisms. Here, we focus on one particular sirtuin, SIRT6. Mice lacking SIRT6 develop a degenerative disorder that in some respects mimics models of accelerated ageing [Cell (2006) 124:315]. We discuss how sirtuins in general and SIRT6 specifically relate to other evolutionarily conserved pathways affecting ageing, and how SIRT6 might function to ensure organismal homeostasis and normal lifespan.
The genetics of ageing: insight from genome‐wide approaches in invertebrate model organisms
Authors: Kennedy B. K. 
Published: August 2010

Abstract.Intense effort has been directed at understanding pathways modulating ageing in invertebrate model organisms. Prior to this decade, several longevity genes had been identified in flies, worms and yeast. More recently, with the development of RNAi libraries in worms and the yeast open reading frame (ORF) deletion collection, it has become routine to perform genome‐wide screens for phenotypes of interest. A number of worm screens have now been performed to identify genes whose reduced expression leads to longer lifespan, and two ORF deletion longevity screens have been performed in yeast. Interestingly, these screens have linked previously unidentified cellular pathways to invertebrate ageing. More surprising, however, is the sheer number of longevity genes in worms and yeast. In this review, I discuss data from genome‐wide screens in the context of evolutionary theories of ageing and raise issues regarding the increasing complexity associated with the genetics of longevity.
Stress‐induced proteolysis in yeast
Authors: Hilt Wolfgang , Wolf Dieter H. 
Published: August 2010

SummarySurvival of cells in their natural environment is crucially dependent on their ability to adapt to constantly occurring changes. The ability of cells to respond to extremes of environmental influences is vital to survival. Proteolysis is a central cellular tool in stress response. Proteins of pathways necessary for normal growth, but harmful under stress conditions, as well as proteins damaged by stress have to be eliminated. The yeast Saccharomyces cerevisiae, a model eukaryote, has evolved two different proteolytic systems: (i) a membrane‐enveloped, vacuolar (lysosomal) system, which contains a variety of non‐specific peptidases and (ii) highly specific peptidases residing at different cellular locations. The best characterized peptidase of the specific system is proteinase yscE, the proteasome equivalent found in all eukaryotic cells. Both the vacuolar and the non‐vacuolar systems are vital components of the stress response in yeast.
The Crl protein activates cryptic genes for curli formation and fibronectin binding in Escherichia coli HB101
Authors: Arnqvist Anna , Olsén Arne , Pfeifer John , Russell David G. , Normark Staffan 
Published: August 2010

SummaryCurli are thin, coiled, temperature‐regulated fibres on fibronectin‐binding Escherichia coli. The subunit protein of curli was highly homologous at its amino terminus to SEF‐17, the subunit protein of thin, aggregative fimbriae of Salmonella enteritidis 27655 strain 3b, suggesting that these fibres form a novel class of surface organelles on enterobacteria. E. coli HB101 is non‐curliated and unable to bind soluble, iodinated fibronectin. The phenotypically cryptic curlin subunit gene, csgA, in HB101 is transcriptionally activated by expressing the cytoplasmic Crl on a multicopy plasmid. Transcriptional activation of csgA by Crl was observed after growth at 26°C but not at 37°C, even though crl transcription was not thermoregulated. A deletion of the 39 carboxy‐terminal residues abolished Crl activity, whereas a deletion of 10 residues at the C‐terminus did not, implying that a region between residue 93 and 122 in the 132‐amino‐acid‐residue large Crl protein is required for activating curli expression in E. coli HB101. crl is a normal housekeeeping gene in E. coli and it is suggested that its gene product may either be a DNA‐binding protein affecting chromatin structure as has been suggested for histone‐like protein H1 or interact with specific regulatory protein(s) controlling transcription of genes required for curli formation and fibronectin binding.
Isolation and characterization of the aadA aminoglycoside‐resistance gene from Salmonella choleraesuis
Authors: Leung K. Y. , Ruschkowski S. R. , Finlay B. B. 
Published: August 2010

SummaryThe streptomycin‐ and spectinomycin‐resistance gene of Salmonella choleraesuis was cloned and its nucleotide sequence determined. The gene is 789 bases long, encoding a protein of a predicted size of 29353 Da. The gene product inactivated streptomycin and spectinomycin by an adenylation modification. It is homologous (c. 40% total identity) to streptomycin adenylyltransferase, a 3′ (9)‐O‐nucleotidyltransferase (AAD(3′)(9)), which is encoded by the aad A gene in Escherichia coli, Agrobacterium tumefaciens, Kiebsiella pneumonia, and Serratia marcescens. The AadA protein of S. choleraesuis differs significantly from the other AadA proteins, indicating that it may have diverged from the other members of this family earlier in evolution. Southern hybridization analysis revealed that homologous aad A sequences were also present in other streptomycin‐resistant Salmonella species.
A new aspect of transcriptional control of the Escherichia coli crp gene: positive autoregulation
Authors: Hanamura Akemi , Aiba Hiroji 
Published: August 2010

SummaryTranscription of the Escherichia coli crp gene is negatively regulated by CRP–cAMP that binds to a specific site located downstream of the crp promoter. A second binding site for CRP–cAMP (CRP site II) exists upstream of the crp promoter. Using an in vitro transcription assay, we have demonstrated that CRP‐cAMP activates transcription of crp in certain conditions. A promoter which carries an altered CRP‐binding site II is no longer activated by CRP–cAMP, indicating that CRP site II mediates the activation of crp transcription. The concentrations of cAMP that are required for positive autoregulation are higher than those for negative autoregulation. Evidence for positive and negative autoregulation in vivo is presented by a quantitative S1 nuclease analysis.
Farnesol and dodecanol effects on the Candida albicans Ras1‐cAMP signalling pathway and the regulation of morphogenesis
Authors: Davis‐Hanna Amber , Piispanen Amy E. , Stateva Lubomira I. , Hogan Deborah A. 
Published: August 2010

Summary Candida albicans hypha formation which has been stimulated via the Ras1‐cAMP‐Efg1 signalling cascade is inhibited by farnesol, a C. albicans autoregulatory factor, and small molecules such as dodecanol. In cultures containing farnesol or dodecanol, hypha formation was restored upon addition of dibutyryl‐cAMP. The CAI4‐Ras1G13V strain, which carries a dominant‐active variant of Ras1 and forms hyphae in the absence of inducing stimuli, grew as yeast in medium with farnesol or dodecanol; the heat shock sensitivity of the CAI4‐Ras1G13V strain was also suppressed by these compounds. Neither Pde1 nor Pde2 was necessary for the repression of hyphal growth by farnesol or dodecanol. Two transcripts, CTA1 and HSP12, which are at higher levels upon mutation of Ras1 or Cdc35, were increased in abundance in cells grown with farnesol or dodecanol. Microscopic analysis of strains carrying CTA1 and HWP1 promoter fusions grown with intermediate concentrations of farnesol or dodecanol indicated a link between cells with the increased expression of cAMP‐repressed genes and cells repressed for hypha formation. Because several cAMP‐controlled outputs are affected by farnesol and dodecanol, our findings suggest that these compounds impact activity of the Ras1‐Cdc35 pathway, thus leading to an alteration of C. albicans morphology.
Co‐ordinated regulation of gluconate catabolism and glucose uptake in Corynebacterium glutamicum by two functionally equivalent transcriptional regulators, GntR1 and GntR2
Authors: Frunzke Julia , Engels Verena , Hasenbein Sonja , Gätgens Cornelia , Bott Michael 
Published: August 2010

Summary Corynebacterium glutamicum is a Gram‐positive soil bacterium that prefers the simultaneous catabolism of different carbon sources rather than their sequential utilization. This type of metabolism requires an adaptation of the utilization rates to the overall metabolic capacity. Here we show how two functionally redundant GntR‐type transcriptional regulators, designated GntR1 and GntR2, co‐ordinately regulate gluconate catabolism and glucose uptake. GntR1 and GntR2 strongly repress the genes encoding gluconate permease (gntP), gluconate kinase (gntK), and 6‐phosphogluconate dehydrogenase (gnd) and weakly the pentose phosphate pathway genes organized in the tkt‐tal‐zwf‐opcA‐devB cluster. In contrast, ptsG encoding the EIIGlc permease of the glucose phosphotransferase system (PTS) is activated by GntR1 and GntR2. Gluconate and glucono‐δ‐lactone interfere with binding of GntR1 and GntR2 to their target promoters, leading to a derepression of the genes involved in gluconate catabolism and reduced ptsG expression. To our knowledge, this is the first example for gluconate‐dependent transcriptional control of PTS genes. A mutant lacking both gntR1 and gntR2 shows a 60% lower glucose uptake rate and growth rate than the wild type when cultivated on glucose as sole carbon source. This growth defect can be complemented by plasmid‐encoded GntR1 or GntR2.
A stepwise model for double‐stranded RNA processing by ribonuclease III
Authors: Gan Jianhua , Shaw Gary , Tropea Joseph E. , Waugh David S. , Court Donald L. , Ji Xinhua 
Published: August 2010

SummaryRNA interference is mediated by small interfering RNAs produced by members of the ribonuclease III (RNase III) family represented by bacterial RNase III and eukaryotic Rnt1p, Drosha and Dicer. For mechanistic studies, bacterial RNase III has been a valuable model system for the family. Previously, we have shown that RNase III uses two catalytic sites to create the 2‐nucleotide (nt) 3′ overhangs in its products. Here, we present three crystal structures of RNase III in complex with double‐stranded RNA, demonstrating how Mg2+is essential for the formation of a catalytically competent protein–RNA complex, how the use of two Mg2+ions can drive the hydrolysis of each phosphodiester bond, and how conformational changes in both the substrate and the protein are critical elements for assembling the catalytic complex. Moreover, we have modelled a protein–substrate complex and a protein–reaction intermediate (transition state) complex on the basis of the crystal structures. Together, the crystal structures and the models suggest a stepwise mechanism for RNase III to execute the phosphoryl transfer reaction.
Haloferax volcanii twin‐arginine translocation substates include secreted soluble, C‐terminally anchored and lipoproteins
Authors: Giménez María I. , Dilks Kieran , Pohlschröder Mechthild 
Published: August 2010

SummaryRecent in silico and in vivo studies have suggested that the majority of proteins destined for secretion in the haloarchaea are trafficked through the twin‐arginine translocation (Tat) pathway. The presence of lipobox motifs in most haloarchaeal Tat signal sequences is intriguing as: (i) bioinformatic searches of archaeal genomes have not identified lipoprotein biogenesis enzymes and (ii) there are no known Tat substrates containing both a twin‐arginine and a bona fide lipobox. We have examined six computationally designated Tat substrates in the haloarchaeon Haloferax volcanii to verify previous computational predictions and to initiate studies of lipoprotein biogenesis via the Tat pathway. Our results confirmed that the six candidate proteins were not only Tat substrates, but also belonged to diverse classes of secretory proteins. Analysis of predicted lipoprotein Tat substrates revealed that they are anchored to the archaeal membrane in a cysteine‐dependent manner. Interestingly, despite the absence of an archaeal lipoprotein signal peptidase II (SPase II) homologue, the SPase II inhibitor globomycin impeded cell growth and specifically prevented maturation of lipoproteins. Together, this work not only represents the first experimental demonstration of a lipoprotein Tat substrate, but also indicates the presence of an unidentified lipoprotein biogenesis pathway in archaea.
Different regions of Mlc and NagC, homologous transcriptional repressors controlling expression of the glucose and N‐acetylglucosamine phosphotransferase systems in Escherichia coli, are required for inducer signal recognition
Authors: Pennetier Carole , Domínguez‐Ramírez Lenin , Plumbridge Jacqueline 
Published: August 2010

SummaryMlc and NagC are two homologous transcription factors which bind to similar DNA targets but for which the inducing signals and mechanisms of activation are very different. Displacing Mlc from its DNA binding sites necessitates its sequestration to the inner membrane via an interaction with PtsG (EIICBGlc), while NagC is displaced from its DNA targets by interacting with GlcNAc6P. We have isolated mutations in both proteins which prevent the inactivation of the repressors by growth on glucose or GlcNAc. These mutations are located in different and specific regions of each protein. For Mlc changes at the C‐terminal make it a constitutive repressor and also prevent it from binding to EIIBGlc. Mutations in NagC, at positions which form a structural motif resembling a glucose binding site in Mlc, produce permanently repressing forms of NagC, suggesting that this motif forms a GlcNAc6P binding site in NagC. The pattern of repression by chimeric proteins of NagC and Mlc confirms the importance of the C‐terminal region of Mlc for both repression and inducer binding and demonstrate that the helix–turn–helix DNA‐binding motif is not sufficient to determine the specificity of interaction of the repressor with DNA.
Periplasmic phosphorylation of lipid A is linked to the synthesis of undecaprenyl phosphate
Authors: Touzé Thierry , Tran An X. , Hankins Jessica V. , Mengin‐Lecreulx Dominique , Trent M. Stephen 
Published: August 2010

SummaryOne‐third of the lipid A found in the Escherichia coli outer membrane contains an unsubstituted diphosphate unit at position 1 (lipid A 1‐diphosphate). We now report an inner membrane enzyme, LpxT (YeiU), which specifically transfers a phosphate group to lipid A, forming the 1‐diphosphate species. 32P‐labelled lipid A obtained from lpxT mutants do not produce lipid A 1‐diphosphate. In vitro assays with Kdo2‐[4′‐32P]lipid A as the acceptor shows that LpxT uses undecaprenyl pyrophosphate as the substrate donor. Inhibition of lipid A 1‐diphosphate formation in wild‐type bacteria was demonstrated by sequestering undecaprenyl pyrophosphate with the cyclic polypeptide antibiotic bacitracin, providing evidence that undecaprenyl pyrophosphate serves as the donor substrate within whole bacteria. LpxT‐catalysed phosphorylation is dependent upon transport of lipid A across the inner membrane by MsbA, a lipid A flippase, indicating a periplasmic active site. In conclusion, we demonstrate a novel pathway in the periplasmic modification of lipid A that is directly linked to the synthesis of undecaprenyl phosphate, an essential carrier lipid required for the synthesis of various bacterial polymers, such as peptidoglycan.