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81.
82.
Background
Overweight and obesity in adulthood are established risk factors for adverse cardiovascular outcomes, but the contribution of overweight in childhood to later cardiovascular risk is less clear. Evidence for a direct effect of childhood overweight would highlight early life as an important target for cardiovascular disease prevention. The aim of this study was to assess whether overweight and obesity in childhood and adolescence contribute to excess cardiovascular risk in adults.Methods and findings
Data from three British birth cohorts, born in 1946, 1958 and 1970, were pooled for analysis (n = 11,447). Individuals were categorised, based on body mass index (BMI), as being of normal weight or overweight/obese in childhood, adolescence and adulthood. Eight patterns of overweight were defined according to weight status at these three stages. Logistic regression models were fitted to assess the associations of patterns of overweight with self-reported type 2 diabetes, hypertension, and coronary heart disease (CHD) in adulthood (34–53 years). Compared to cohort members who were never overweight, those who were obese in adulthood had increased risk of all outcomes. For type 2 diabetes, the odds ratio was higher for obese adults who were also overweight or obese in childhood and adolescence (OR 12.6; 95% CI 6.6 to 24.0) than for those who were obese in adulthood only (OR 5.5; 95% CI 3.4 to 8.8). There was no such effect of child or adolescent overweight on hypertension. For CHD, there was weak evidence of increased risk among those with overweight in childhood. The main limitations of this study concern the use of self-reported outcomes and the generalisability of findings to contemporary child populations.Conclusions
Type 2 diabetes and to a lesser extent CHD risk may be affected by overweight at all stages of life, while hypertension risk is associated more strongly with weight status in adulthood. 相似文献83.
Mass spectrometry-based studies of proteins that are post-translationally modified by O-linked β-N-acetylglucosamine (O-GlcNAc) are challenged in effectively identifying the sites of modification while simultaneously sequencing the peptides. Here we tested the hypothesis that a combination of high-energy C-trap dissociation (HCD) and electron transfer dissociation (ETD) could specifically target the O-GlcNAc modified peptides and elucidate the amino acid sequence while preserving the attached GlcNAc residue for accurate site assignment. By taking advantage of the recently characterized O-GlcNAc-specific IgG monoclonal antibodies and the combination of HCD and ETD fragmentation techniques, O-GlcNAc modified proteins were enriched from HEK293T cells and subsequently characterized using the LTQ Orbitrap Velos ETD (Thermo Fisher Scientific) mass spectrometer. In our data set, 83 sites of O-GlcNAc modification are reported with high confidence confirming that the HCD/ETD combined approach is amenable to the detection and site assignment of O-GlcNAc modified peptides. Realizing HCD triggered ETD fragmentation on a linear ion trap/Orbitrap platform for more in-depth analysis and application of this technique to other post-translationally modified proteins are currently underway. Furthermore, this report illustrates that the O-GlcNAc transferase appears to demonstrate promiscuity with regards to the hydroxyl-containing amino acid modified in short stretches of primary sequence of the glycosylated polypeptides. 相似文献
84.
Simon E Brill Anant RC Patel Richa Singh Alexander J Mackay Jeremy S Brown John R Hurst 《Respiratory research》2015,16(1)
Background
Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described.The purpose of this study was to describe changes in lung function, symptoms, health status and inflammation during the development and recovery from community-treated exacerbations.Methods
This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values.Results
At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset.Conclusion
Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0167-9) contains supplementary material, which is available to authorized users. 相似文献85.
Reassembly of flagellar B (alpha beta) tubulin into singlet microtubules: consequences for cytoplasmic microtubule structure and assembly 下载免费PDF全文
B(alpha beta) tubulin was obtained from a homogeneous class of microtubules, the incomplete B subfiber of sea urchin sperm flagellar doublet microtubules, by thermal fractionation. The thermally derived soluble B tubulin fraction (100, 000 g-h) repolymerizes in vitro, yielding microtubule-like structures. The microtubule-associated protein (MAP) composition and certain assembly parameters of thermally derived B tubulin are different from those reported for sonication- derived flageller tubulin and purified vertebrate tubulin. The "microtubules" reassembled from thermally prepared B tubulin are composed of 12-15 protofilaments (73% possess 14 protofilaments). A certain number possess a single "adlumenal component" applied to their inside walls, regardless of the number of protofilaments. Following the first cycle of polymerization, 81% of the B tubulin and essentially 100% of the MAPs remain cold insoluble. Evidence suggests that B tubulin assembles faithfully into a B lattice, creating a j seam between two protofilaments that are laterally bonded in a A-lattice configuration. The significance of these seams is discussed in relation to the mechanism of microtubule assembly, the stability of observed ribbons of protofilaments, and the three-dimensional organization of microtubule-associated components. 相似文献
86.
A model of the carbohydrate recognition domain CRD, residues 111-245, of
hamster galectin-3 has been made using homology modeling and dynamics
minimization methods. The model is based on the known x-ray structures of
bovine galectin-1 and human galectin-2. The oligosaccharides
NeuNAc-alpha2,3-Gal-beta1,4-Glc and GalNAc-alpha1, 3-
[Fuc-alpha1,2]-Gal-beta1,4-Glc, known to be specific high-affinity ligands
for galectin-3, as well as lactose recognized by all galectins were docked
in the galectin-3 CRD model structure and a minimized binding conformation
found in each case. These studies indicate a putative extended
carbohydrate-binding subsite in the hamster galectin- 3 involving Arg139,
Glu230, and Ser232 for NeuNAc-alpha2,3-; Arg139 and Glu160 for
fucose-alpha1,2-; and Arg139 and Ile141 for GalNAc-alpha1,3- substituents
on the primary galactose. Each of these positions is variable within the
whole galectin family. Two of these residues, Arg139 and Ser232, were
selected for mutagenesis to probe their importance in this newly identified
putative subsite. Residue 139 adopts main-chain dihedral angles
characteristic of an isolated bridge structural feature, while residue 232
is the C-terminal residue of beta- strand-11, and is followed immediately
by an inverse gamma-turn. A systematic series of mutant proteins have been
prepared to represent the residue variation present in the aligned
sequences of galectins-1, - 2, and -3. Minimized docked models were
generated for each mutant in complex with NeuNAc-alpha2,3-Gal-beta1,4-Glc,
GalNAc-alpha1, 3-[Fuc- alpha1,2]-Gal-beta1,4- Glc, and Gal-beta1,4-Glc.
Correlation of the computed protein-carbohydrate interaction energies for
each lectin- oligosaccharide pair with the experimentally determined
binding affinities for fetuin and asialofetuin or the relative potencies of
lactose and sialyllactose in inhibiting binding to asiolofetuin is
consistent with the postulated key importance of Arg139 in recognition of
the extended sialylated ligand.
相似文献
87.
Glynn SE Baker PJ Sedelnikova SE Davies CL Eadsforth TC Levy CW Rodgers HF Blackburn GM Hawkes TR Viner R Rice DW 《Structure (London, England : 1993)》2005,13(12):1809-1817
The structure of A. thaliana imidazoleglycerol-phosphate dehydratase, an enzyme of histidine biosynthesis and a target for the triazole phosphonate herbicides, has been determined to 3.0 A resolution. The structure is composed of 24 identical subunits arranged in 432 symmetry and shows how the formation of a novel dimanganese cluster is crucial to the assembly of the active 24-mer from an inactive trimeric precursor and to the formation of the active site of the enzyme. Molecular modeling suggests that the substrate is bound to the manganese cluster as an imidazolate moiety that subsequently collapses to yield a diazafulvene intermediate. The mode of imidazolate recognition exploits pseudosymmetry at the active site arising from a combination of the assembly of the particle and the pseudosymmetry present in each subunit as a result of gene duplication. This provides an intriguing example of the role of evolution in the design of Nature's catalysts. 相似文献
88.
Java language has been demonstrated to be an effective tool in supporting medical image viewing in Russia. This evaluation was completed by obtaining a maximum of 20 images, depending on the client's computer workstation from one patient using a commercially available computer tomography (CT) scanner. The images were compared against standard CT images that were viewed at the site of capture. There was no appreciable difference. The client side is a lightweight component that provides an intuitive interface for end users. Each image is loaded in its own thread and the user can begin work after the first image has been loaded. This feature is especially useful on slow connection speed, 9.6 Kbps for example. The server side, which is implemented by the Java Servlet Engine works more effective than common gateway interface (CGI) programs do. Advantages of the Java Technology place this program on the next level of application development. This paper presents a unique application of Java in telemedicine. 相似文献
89.
ObjectiveTo assess the function of the new system of review by multicentre research ethics committees and to highlight areas where improvement is still needed.DesignProspectively collected data from a multicentre study was examined with respect to the ethics review process. Administrative, financial, and time elements of the review process were audited.SettingA single multicentre research ethics committee and 125 local ethics committees from six regions of England.ResultsOnly 40% of local ethics committees considered our study in the manner specified in the 1998 directive. Less than a third of committees replied within the 21 day period stipulated, although committees acting by executive subcommittee replied more quickly than those not acting by executive subcommittee. There was a tendency for executive subcommittees to approve studies in a shorter time. Local ethics committees asked for a large number of non-local changes to the application. The financial cost of applying to multiple ethics committees remains high, mainly because multiple copies of research applications are being requested.ConclusionsThe new system of approval by multicentre research ethics committee for multicentre studies was introduced to reduce administrative costs, speed up the process of reviews by multiple research ethics committees, and standardise the conclusions of the local research ethics committees. Since its introduction an improvement has been seen, but the system is not yet universally functioning as intended. Ethics review still remains a hindrance to the financial resources and commencement of national studies. We strongly support the structure of review by multicentre research ethics committees but suggest that the system has yet to achieve its aims. 相似文献
90.
Elisangela F Silva Mariana Orsi ?ngela L Andrade Rosana Z Domingues Breno M Silva Helena RC de Araújo Paulo FP Pimenta Michael S Diamond Eliseu SO Rocha Erna G Kroon Luiz CC Malaquias Luiz FL Coelho 《Journal of nanobiotechnology》2012,10(1):1-5