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51.
Background
Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood.This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation.Methods
Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand.Results
MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P < 0.01). TIMP-1 levels decreased from 3.5 μg/g [0.6 to 7.8] to 1.5 μg/g [0.3 to 4.9] (P = 0.16). MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05). Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05). Macrophage numbers remained level. MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01).Conclusion
During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline. 相似文献52.
In order to reconstruct phylogenetic trees from extremely dissimilar
sequences it is necessary to estimate accurately the extent of sequence
divergence. In this paper a new method of sequence analysis, Markov triple
analysis, is developed for determining the relative frequencies of
nucleotide substitutions within the three branches of a three-taxon
dendrogram. Assuming that nucleotide sites are independently and
identically distributed and assuming a Markov model for nucleotide (or
protein) evolution, it is shown that the unique Markov matrices can be
reconstructed given only the joint probability distribution relating three
taxa. (In the much simpler case involving only two taxa and two character
states, Markov matrices can also be reconstructed, provided symmetry
assumptions are placed on the elements of the matrices.) The method is
illustrated using sequence data from the combined first and second codon
positions derived from complete human, mouse, and cow mitochondrial
sequences.
相似文献
53.
DNA hybridization evidence for the principal lineages of hummingbirds (Aves:Trochilidae) 总被引:3,自引:0,他引:3
The spectacular evolutionary radiation of hummingbirds (Trochilidae) has
served as a model system for many biological studies. To begin to provide a
historical context for these investigations, we generated a complete matrix
of DNA hybridization distances among 26 hummingbirds and an outgroup swift
(Chaetura pelagica) to determine the principal hummingbird lineages. FITCH
topologies estimated from symmetrized delta TmH-C values and subjected to
various validation methods (bootstrapping, weighted jackknifing, branch
length significance) indicated a fundamental split between hermit
(Eutoxeres aquila, Threnetes ruckeri; Phaethornithinae) and nonhermit
(Trochilinae) hummingbirds, and provided strong support for six principal
nonhermit clades with the following branching order: (1) a predominantly
lowland group comprising caribs (Eulampis holosericeus) and relatives
(Androdon aequatorialis and Heliothryx barroti) with violet-ears (Colibri
coruscans) and relatives (Doryfera ludovicae); (2) an Andean-associated
clade of highly polytypic taxa (Eriocnemis, Heliodoxa, and Coeligena); (3)
a second endemic Andean clade (Oreotrochilus chimborazo, Aglaiocercus
coelestis, and Lesbia victoriae) paired with thorntails (Popelairia
conversii); (4) emeralds and relatives (Chlorostilbon mellisugus, Amazilia
tzacatl, Thalurania colombica, Orthorhyncus cristatus and Campylopterus
villaviscensio); (5) mountain-gems (Lampornis clemenciae and Eugenes
fulgens); and (6) tiny bee-like forms (Archilochus colubris, Myrtis fanny,
Acestrura mulsant, and Philodice mitchellii). Corresponding analyses on a
matrix of unsymmetrized delta values gave similar support for these
relationships except that the branching order of the two Andean clades (2,
3 above) was unresolved. In general, subsidiary relationships were
consistent and well supported by both matrices, sometimes revealing
surprising associations between forms that differ dramatically in plumage
and bill morphology. Our results also reveal some basic aspects of
hummingbird ecologic and morphologic evolution. For example, most of the
diverse endemic Andean assemblage apparently comprises two genetically
divergent clades, whereas the majority of North American hummingbirds
belong a single third clade. Genetic distances separating some
morphologically distinct genera (Oreotrochilus, Aglaiocercus, Lesbia;
Myrtis, Acestrura, Philodice) were no greater than among congeneric
(Coeligena) species, indicating that, in hummingbirds, morphological
divergence does not necessarily reflect level of genetic divergence.
相似文献
54.
E C Castro JA Diaz GomezDe Ferreyra C R De Castro N D'Acosta C M De Fenos 《Biochemical and biophysical research communications》1973,50(2):337-343
There is a higher activity of ethyl morphine N-demethylase (EM-ase) and cytochrome P-450 (P-450) reductase as well as higher P-450 content in the smooth endoplasmic reticulum (SER) than in the rough endoplasmic reticulum (RER). The extent of the irreversible binding of the14C from14CCl4 to lipids and proteins, as well as the CCl4-induced destruction of P-450 is more intense in SER than in RER while the opposite was found for glucose 6-phosphatase (G6P-ase) destruction. CCl4-induced lipid peroxidation is as intense in SER as is in RER.14C from14CCl4 gets irreversibly bound to ribosomal proteins. 相似文献
55.
Peter Thorpe Sophie Mantelin Peter JA Cock Vivian C Blok Mirela C Coke Sebastian Eves-van den Akker Elena Guzeeva Catherine J Lilley Geert Smant Adam J Reid Kathryn M Wright Peter E Urwin John T Jones 《BMC genomics》2014,15(1)
Background
The potato cyst nematode Globodera pallida has biotrophic interactions with its host. The nematode induces a feeding structure – the syncytium – which it keeps alive for the duration of the life cycle and on which it depends for all nutrients required to develop to the adult stage. Interactions of G. pallida with the host are mediated by effectors, which are produced in two sets of gland cells. These effectors suppress host defences, facilitate migration and induce the formation of the syncytium.Results
The recent completion of the G. pallida genome sequence has allowed us to identify the effector complement from this species. We identify 128 orthologues of effectors from other nematodes as well as 117 novel effector candidates. We have used in situ hybridisation to confirm gland cell expression of a subset of these effectors, demonstrating the validity of our effector identification approach. We have examined the expression profiles of all effector candidates using RNAseq; this analysis shows that the majority of effectors fall into one of three clusters of sequences showing conserved expression characteristics (invasive stage nematode only, parasitic stage only or invasive stage and adult male only). We demonstrate that further diversity in the effector pool is generated by alternative splicing. In addition, we show that effectors target a diverse range of structures in plant cells, including the peroxisome. This is the first identification of effectors from any plant pathogen that target this structure.Conclusion
This is the first genome scale search for effectors, combined to a life-cycle expression analysis, for any plant-parasitic nematode. We show that, like other phylogenetically unrelated plant pathogens, plant parasitic nematodes deploy hundreds of effectors in order to parasitise plants, with different effectors required for different phases of the infection process.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-923) contains supplementary material, which is available to authorized users. 相似文献56.
Daiane D Hartwig Thaís L Oliveira Fabiana K Seixas Karine M Forster Caroline Rizzi Cláudia P Hartleben Alan JA McBride Odir A Dellagostin 《Microbial cell factories》2010,9(1):98
Background
Leptospirosis, a zoonosis caused by Leptospira spp., is recognized as an emergent infectious disease. Due to the lack of adequate diagnostic tools, vaccines are an attractive intervention strategy. Recombinant proteins produced in Escherichia coli have demonstrated promising results, albeit with variable efficacy. Pichia pastoris is an alternative host with several advantages for the production of recombinant proteins. 相似文献57.
Lucas A Smolders Bj?rn P Meij David Onis Frank M Riemers Niklas Bergknut Richard Wubbolts Guy CM Grinwis Martin Houweling Marian JA Groot Koerkamp Dik van Leenen Frank CP Holstege Herman AW Hazewinkel Laura B Creemers Louis C Penning Marianna A Tryfonidou 《Arthritis research & therapy》2013,15(1):R23
Introduction
Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration.Methods
Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knock-out mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age.Results
Early IVD degeneration involved significant changes in numerous pathways, including Wnt/β-catenin signaling. With regard to Wnt/β-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant down-regulation of axin2 gene expression. IVD degeneration involved significant down-regulation in Caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of wild-type mice was rich in viable NCs, whereas the NP of Caveolin-1 knock-out mice contained chondroid-like matrix with mainly apoptotic, small, rounded cells.Conclusions
Early IVD degeneration involves down-regulation of canonical Wnt signaling and Caveolin-1 expression, which appears to be essential to the physiology and preservation of NCs. Therefore, Caveolin-1 may be regarded an exciting target for developing strategies for IVD regeneration. 相似文献58.
Background
High-throughput genotype (HTG) data has been used primarily in genome-wide association (GWA) studies; however, GWA results explain only a limited part of the complete genetic variation of traits. In systems genetics, network approaches have been shown to be able to identify pathways and their underlying causal genes to unravel the biological and genetic background of complex diseases and traits, e.g., the Weighted Gene Co-expression Network Analysis (WGCNA) method based on microarray gene expression data. The main objective of this study was to develop a scale-free weighted genetic interaction network method using whole genome HTG data in order to detect biologically relevant pathways and potential genetic biomarkers for complex diseases and traits.Results
We developed the Weighted Interaction SNP Hub (WISH) network method that uses HTG data to detect genome-wide interactions between single nucleotide polymorphism (SNPs) and its relationship with complex traits. Data dimensionality reduction was achieved by selecting SNPs based on its: 1) degree of genome-wide significance and 2) degree of genetic variation in a population. Network construction was based on pairwise Pearson's correlation between SNP genotypes or the epistatic interaction effect between SNP pairs. To identify modules the Topological Overlap Measure (TOM) was calculated, reflecting the degree of overlap in shared neighbours between SNP pairs. Modules, clusters of highly interconnected SNPs, were defined using a tree-cutting algorithm on the SNP dendrogram created from the dissimilarity TOM (1-TOM). Modules were selected for functional annotation based on their association with the trait of interest, defined by the Genome-wide Module Association Test (GMAT). We successfully tested the established WISH network method using simulated and real SNP interaction data and GWA study results for carcass weight in a pig resource population; this resulted in detecting modules and key functional and biological pathways related to carcass weight.Conclusions
We developed the WISH network method which is a novel 'systems genetics' approach to study genetic networks underlying complex trait variation. The WISH network method reduces data dimensionality and statistical complexity in associating genotypes with phenotypes in GWA studies and enables researchers to identify biologically relevant pathways and potential genetic biomarkers for any complex trait of interest.59.
Reina JA de Kinderen Danielle AJE Lambrechts Debby Postulart Alfons GH Kessels Jos GM Hendriksen Albert P Aldenkamp Marian HJM Majoie 《BMC neurology》2011,11(1):10
Background
Epilepsy is a neurological disorder, characterized by recurrent unprovoked seizures which have a high impact on the individual as well as on society as a whole. In addition to the economic burden, epilepsy imposes a substantial burden on the patients and their surroundings. Patients with uncontrolled epilepsy depend heavily on informal care and on health care professionals. About 30% of patients suffer from drug-resistant epilepsy. The ketogenic diet can be a treatment of last resort, especially for children. The beneficial effect of the ketogenic diet has been proven, but information is lacking about its cost-effectiveness. In the current study we will evaluate the (cost-) effectiveness of the ketogenic diet in children and adolescents with intractable epilepsy. 相似文献60.
PAWEŁ JAŁOSZYŃSKI 《Systematic Entomology》2012,37(3):448-477
Neotropical genera of Cephenniini characterized by an additional leg ‘segment’ (‘trochantellus’) are revised, and the following new taxa are described: Shyri gen.n. , Shyri pichincha sp.n. (type species of Shyri) (Ecuador), Shyri perversus sp.n. (Ecuador), Shyri quitu sp.n. (Ecuador), Shyri microphthalmus sp.n. (Ecuador), Monstrophennium gen.n. (type species: Cephennium spinicolle Schaufuss), Furcodes gen.n. , Furcodes apicalis sp.n. (type species of Furcodes) (Mexico), Furcodes tutule sp.n. (Honduras), Paracephennium pumilio sp.n. (Costa Rica), Pseudocephennium iwokramanum sp.n. (Guyana), Pseudocephennium trilineatum sp.n. (Guyana), Pseudocephennium araguanum sp.n. (Venezuela), Pseudocephennium maximum sp.n. (Venezuela), Pseudocephennium peruvianum sp.n. (Peru), Pseudocephennium cochabambanum sp.n. (Bolivia), Pseudocephennium saramaccanum sp.n. (Suriname) and Pseudocephennium brokopondonum sp.n. (Suriname). Pseudocephennium spinicolle (Schaufuss) is transferred to Monstrophennium. Cladistic analysis of characters from adult morphology of all genera of Cephenniini and a large outgroup sample from Cyrtoscydmini, Eutheiini, Scydmaenini, Clidicini and Mastigini strongly supported the monophyly of Cephenniini. However, only the Cephennomicrus group comprising nine genera was strongly supported as a monophyletic clade, while only weak support was found for the previously suggested Cephennodes group and Cephennium group. Two alternative hypotheses concerning the phylogeny of Cephenniini are put forward and discussed: (i) the Cephennium group is sister to all remaining Cephenniini; or (ii) the Cephennomicrus group is sister to all remaining Cephenniini. The Neotropical genera with ‘trochantellus’ form a well‐supported clade derived from the ancestral lineage of the Cephennodes group. 相似文献