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91.
Petersen AM Magkos F Atherton P Selby A Smith K Rennie MJ Pedersen BK Mittendorfer B 《American journal of physiology. Endocrinology and metabolism》2007,293(3):E843-E848
Smoking causes multiple organ dysfunction. The effect of smoking on skeletal muscle protein metabolism is unknown. We hypothesized that the rate of skeletal muscle protein synthesis is depressed in smokers compared with non-smokers. We studied eight smokers (> or =20 cigarettes/day for > or =20 years) and eight non-smokers matched for sex (4 men and 4 women per group), age (65 +/- 3 and 63 +/- 3 yr, respectively; means +/- SEM) and body mass index (25.9 +/- 0.9 and 25.1 +/- 1.2 kg/m(2), respectively). Each subject underwent an intravenous infusion of stable isotope-labeled leucine in conjunction with blood and muscle tissue sampling to measure the mixed muscle protein fractional synthesis rate (FSR) and whole body leucine rate of appearance (Ra) in plasma (an index of whole body proteolysis), the expression of genes involved in the regulation of muscle mass (myostatin, a muscle growth inhibitor, and MAFBx and MuRF-1, which encode E3 ubiquitin ligases in the proteasome proteolytic pathway) and that for the inflammatory cytokine TNF-alpha in muscle, and the concentration of inflammatory markers in plasma (C-reactive protein, TNF-alpha, interleukin-6) which are associated with muscle wasting in other conditions. There were no differences between nonsmokers and smokers in plasma leucine concentration, leucine rate of appearance, and plasma concentrations of inflammatory markers, or TNF-alpha mRNA in muscle, but muscle protein FSR was much less (0.037 +/- 0.005 vs. 0.059 +/- 0.005%/h, respectively, P = 0.004), and myostatin and MAFBx (but not MuRF-1) expression were much greater (by approximately 33 and 45%, respectivley, P < 0.05) in the muscle of smokers than of nonsmokers. We conclude that smoking impairs the muscle protein synthesis process and increases the expression of genes associated with impaired muscle maintenance; smoking therefore likely increases the risk of sarcopenia. 相似文献
92.
Selby Katherine A. Roe Helen M. Wright Alexander J. van de Plassche Orson Derrett Sally R. 《Vegetation History and Archaeobotany》2022,31(2):137-154
Vegetation History and Archaeobotany - Pollen and plant macrofossils are often well-preserved in coastal sediments, providing a palaeoenvironmental record of sea-level and landscape change. In this... 相似文献
93.
Letícia Muraro Wildner Maria Luiza Bazzo Susie Coutinho Liedke Christiane Louren?o Nogueira Gabriela Segat Simone Gon?alves Senna Aline Daiane Schlindwein Jaquelline Germano de Oliveira Darcita B Rovaris Claudio A Bonjardim Erna G Kroon Paulo CP Ferreira 《Memórias do Instituto Oswaldo Cruz》2014,109(3):356-361
The identification of mycobacteria is essential because tuberculosis (TB) and
mycobacteriosis are clinically indistinguishable and require different therapeutic
regimens. The traditional phenotypic method is time consuming and may last up to 60
days. Indeed, rapid, affordable, specific and easy-to-perform identification methods
are needed. We have previously described a polymerase chain reaction-based method
called a mycobacteria mobility shift assay (MMSA) that was designed for
Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria
(NTM) species identification. The aim of this study was to assess the MMSA for the
identification of MTC and NTM clinical isolates and to compare its performance with
that of the PRA-hsp65 method. A total of 204 clinical isolates (102
NTM and 102 MTC) were identified by the MMSA and PRA-hsp65. For
isolates for which these methods gave discordant results, definitive species
identification was obtained by sequencing fragments of the 16S rRNA and
hsp65 genes. Both methods correctly identified all MTC isolates. Among
the NTM isolates, the MMSA alone assigned 94 (92.2%) to a complex or species, whereas
the PRA-hsp65 method assigned 100% to a species. A 91.5% agreement
was observed for the 94 NTM isolates identified by both methods. The MMSA provided
correct identification for 96.8% of the NTM isolates compared with 94.7% for
PRA-hsp65. The MMSA is a suitable auxiliary method for routine
use for the rapid identification of mycobacteria. 相似文献
94.
Nicholas M. Selby Nitin V. Kolhe Christopher W. McIntyre John Monaghan Nigel Lawson David Elliott Rebecca Packington Richard J. Fluck 《PloS one》2012,7(11)
Background
The high mortality rates that follow the onset of acute kidney injury (AKI) are well recognised. However, the mode of death in patients with AKI remains relatively under-studied, particularly in general hospitalised populations who represent the majority of those affected. We sought to describe the primary cause of death in a large group of prospectively identified patients with AKI.Methods
All patients sustaining AKI at our centre between 1st October 2010 and 31st October 2011 were identified by real-time, hospital-wide, electronic AKI reporting based on the Acute Kidney Injury Network (AKIN) diagnostic criteria. Using this system we are able to generate a prospective database of all AKI cases that includes demographic, outcome and hospital coding data. For those patients that died during hospital admission, cause of death was derived from the Medical Certificate of Cause of Death.Results
During the study period there were 3,930 patients who sustained AKI; 62.0% had AKI stage 1, 20.6% had stage 2 and 17.4% stage 3. In-hospital mortality rate was 21.9% (859 patients). Cause of death could be identified in 93.4% of cases. There were three main disease categories accounting for three quarters of all mortality; sepsis (41.1%), cardiovascular disease (19.2%) and malignancy (12.9%). The major diagnosis leading to sepsis was pneumonia, whilst cardiovascular death was largely a result of heart failure and ischaemic heart disease. AKI was the primary cause of death in only 3% of cases.Conclusions
Mortality associated with AKI remains high, although cause of death is usually concurrent illness. Specific strategies to improve outcomes may therefore need to target not just the management of AKI but also the most relevant co-existing conditions. 相似文献95.
The photolyase/cryptochrome family of proteins are FAD-containing flavoproteins which carry out blue-light-dependent functions including DNA repair, plant growth and development, and regulation of the circadian clock. In addition to FAD, many members of the family contain a second chromophore which functions as a photo-antenna, harvesting light and transferring the excitation energy to FAD and thus increasing the efficiency of the system. The second chromophore is methenyltetrahydrofolate (MTHF) in most photolyases characterized to date and FAD, FMN, or 5-deazariboflavin in others. To date, no second chromophore has been identified in cryptochromes. Drosophila contains three members of the cryptochrome/photolyase family: cyclobutane pyrimidine dimer (CPD) photolyase, (6-4) photoproduct photolyase, and cryptochrome. We developed an expression system capable of incorporating all known second chromophores into the cognate cryptochrome/photolyase family members. Using this system, we demonstrate that Drosophila CPD photolyase and (6-4) photolyase employ 5-deazariboflavin as their second chromophore, but Drosophila cryptochrome, which is evolutionarily closer to (6-4) photolyase than the CPD photolyase, lacks a second chromophore. 相似文献
96.
Inhaled adenosine A(2A) receptor agonists for the treatment of chronic obstructive pulmonary disease
Mantell SJ Stephenson PT Monaghan SM Maw GN Trevethick MA Yeadon M Keir RF Walker DK Jones RM Selby MD Batchelor DV Rozze S Chavaroche H Hobson TJ Dodd PG Lemaitre A Wright KN Stuart EF 《Bioorganic & medicinal chemistry letters》2008,18(4):1284-1287
COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. A strategy of minimizing side-effect liability by maximizing systemic clearance was followed and pharmacological and pharmacokinetic SAR of a series of inhaled A(2A) agonists described. A sevenfold improvement in potency and 150-fold reduction in side-effect liability over the lead compound CGS-21680, were obtained. 相似文献
97.
David A Cairns David N Perkins Anthea J Stanley Douglas Thompson Jennifer H Barrett Peter J Selby Rosamonde E Banks 《BMC bioinformatics》2008,9(1):1-19
Background
Evolutionary conservation of RNA secondary structure is a typical feature of many functional non-coding RNAs. Since almost all of the available methods used for prediction and annotation of non-coding RNA genes rely on this evolutionary signature, accurate measures for structural conservation are essential.Results
We systematically assessed the ability of various measures to detect conserved RNA structures in multiple sequence alignments. We tested three existing and eight novel strategies that are based on metrics of folding energies, metrics of single optimal structure predictions, and metrics of structure ensembles. We find that the folding energy based SCI score used in the RNAz program and a simple base-pair distance metric are by far the most accurate. The use of more complex metrics like for example tree editing does not improve performance. A variant of the SCI performed particularly well on highly conserved alignments and is thus a viable alternative when only little evolutionary information is available. Surprisingly, ensemble based methods that, in principle, could benefit from the additional information contained in sub-optimal structures, perform particularly poorly. As a general trend, we observed that methods that include a consensus structure prediction outperformed equivalent methods that only consider pairwise comparisons.Conclusion
Structural conservation can be measured accurately with relatively simple and intuitive metrics. They have the potential to form the basis of future RNA gene finders, that face new challenges like finding lineage specific structures or detecting mis-aligned sequences. 相似文献98.
Marcilio CP de Souto Ivan G Costa Daniel SA de Araujo Teresa B Ludermir Alexander Schliep 《BMC bioinformatics》2008,9(1):497
Background
The use of clustering methods for the discovery of cancer subtypes has drawn a great deal of attention in the scientific community. While bioinformaticians have proposed new clustering methods that take advantage of characteristics of the gene expression data, the medical community has a preference for using "classic" clustering methods. There have been no studies thus far performing a large-scale evaluation of different clustering methods in this context. 相似文献99.
The significant potential of tissue-based proteomic biomarker studies can be restricted by difficulties in accessing samples in optimal fresh-frozen form. While archival formalin-fixed tissue collections with attached clinical and outcome data represent a valuable alternate resource, the use of formalin as a fixative which induces protein cross-linking, has generally been assumed to render them unsuitable for proteomic studies. However, this view has been challenged recently with the publication of several papers accomplishing variable degrees of heat-induced reversal of cross-links. Although still in its infancy and requiring the quantitative optimisation of several critical parameters, formalin-fixed tissue proteomics holds promise as a powerful tool for biomarker-driven translational research. Here, we critically review the current status of research in the field, highlighting challenges which need to be addressed for robust quantitative application of protocols to ensure confident high impact inferences can be made. 相似文献
100.