The role bacteria play in the progression of COPD has increasingly been highlighted in recent years. However, the microbial community complexity in the lower airways of patients with COPD is poorly ...characterised.
To compare the lower airway microbiota in patients with COPD, smokers and non-smokers.
Bronchial wash samples from adults with COPD (n=18), smokers with no airways disease (n=8) and healthy individuals (n=11) were analysed by extended-culture and culture-independent Illumina MiSeq sequencing. We determined aerobic and anaerobic microbiota load and evaluated differences in bacteria associated with the three cohorts. Culture-independent analysis was used to determine differences in microbiota between comparison groups including taxonomic richness, diversity, relative abundance, 'core' microbiota and co-occurrence.
Extended-culture showed no difference in total load of aerobic and anaerobic bacteria between the three cohorts. Culture-independent analysis revealed that the prevalence of members of Pseudomonas spp. was greater in the lower airways of patients with COPD; however, the majority of the sequence reads for this taxa were attributed to three patients. Furthermore, members of Bacteroidetes, such as Prevotella spp., were observed to be greater in the 'healthy' comparison groups. Community diversity (α and β) was significantly less in COPD compared with healthy groups. Co-occurrence of bacterial taxa and the observation of a putative 'core' community within the lower airways were also observed.
Microbial community composition in the lower airways of patients with COPD is significantly different to that found in smokers and non-smokers, indicating that a component of the disease is associated with changes in microbiological status.
The recent detection of a neutron star merger by the LIGO collaboration has renewed interest in laboratory studies of r-process elements. Accurate modeling and interpretation of the electromagnetic ...transients following the mergers requires computationally expensive calculations of both the structure and opacity of all trans-iron elements. To date, the necessary atomic data to benchmark structure codes are incomplete or, in some cases, absent entirely. Within the available laboratory studies, the literature on Au i and Au ii provides incomplete reports of the emission lines and level structures. We present a new study of Au i and Au ii lines and levels by exposing a solid gold target to plasma in the Compact Toroidal Hybrid (CTH) experiment at Auburn University. A wavelength range from 187 to 800 nm was studied. In Au i, 86 lines are observed, 43 of which are unreported in the literature, and the energies of 18 levels and 16 of the 18 known levels are corroborated by a least-squares level energy optimization. In Au ii, 76 emission lines are observed, and 51 of the lines are unreported in the literature. For both Au i and Au ii, the new lines predominantly originate from the most energetic of the known levels, and over half of the new Au ii lines have wavelengths longer than 300 nm. For the estimated electron parameters of CTH plasmas at the gold target (ne ∼ 1012 cm−3, Te ∼ 10 eV), two-electron transitions are similar in intensity to LS-allowed one-electron transitions.
Two Cu(II) metal–organic frameworks (MOFs) were prepared on the nanoscale at room temperature using a microemulsion method, namely, Cu3(BTC)2(H2O)3 (BTC = benzene-1,3,5-tricarboxylate), known as ...HKUST-1 (1), and Cu2(OH)(BTC)(H2O)·2H2O (2). Thermochemical and gas sorption properties of the microporous topologies were characterized by mid- and far-infrared vibrational spectroscopy, supported by periodic density functional theory calculations. The mid-infrared profile of 1 appeared altered in response to gas sorption under variable temperature and pressure conditions. Vibrational mode analysis indicated the most sensitive infrared peaks were associated with the internal vibrations of organic linker moieties indirectly coupled to the Cu(II)–gas coordination site, activated by a lowered symmetry induced by guest interactions. Synchrotron far-infrared spectroscopy was shown to be a useful diagnostic for the microstructure of 1 and 2 where different temperature dependences were displayed in the low-frequency region. The loss of residual water during the activation of 2 at elevated temperature coincides with peaks indicative of free paddle-wheel moieties emerging in the far-IR spectra. As demonstrated for both materials 1 and 2, vibrational mode analysis was effective in screening MOF materials for their propensity toward gas uptake and, inversely, the diffusion of guest species such as adsorbed water from the microporous environments.
While post-transcriptional control is thought to be required at the periphery of neurons and glia, its extent is unclear. Here, we investigate systematically the spatial distribution and expression ...of mRNA at single molecule sensitivity and their corresponding proteins of 200 YFP trap lines across the intact Drosophila nervous system. 97.5% of the genes studied showed discordance between the distribution of mRNA and the proteins they encode in at least one region of the nervous system. These data suggest that post-transcriptional regulation is very common, helping to explain the complexity of the nervous system. We also discovered that 68.5% of these genes have transcripts present at the periphery of neurons, with 9.5% at the glial periphery. Peripheral transcripts include many potential new regulators of neurons, glia, and their interactions. Our approach is applicable to most genes and tissues and includes powerful novel data annotation and visualization tools for post-transcriptional regulation.
Background and Purpose
NF‐κB‐driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA3) is a plant‐derived diterpenoid with documented anti‐inflammatory ...activity, which is reported to induce A20‐like zinc finger proteins in plants. Here, we sought to investigate the anti‐inflammatory effect of GA3 in airway epithelial cells and determine if the anti‐inflammatory action relates to A20 induction.
Experimental Approach
Primary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o‐) were used. Cells were pre‐incubated with GA3, stimulated with Pseudomonas aeruginosa LPS; IL‐6 and IL‐8 release, A20, NF‐κB and IκBα expression were then evaluated. To determine if any observed anti‐inflammatory effect occurred via an A20‐dependent mechanism, A20 was silenced using siRNA.
Key Results
Cells pre‐incubated with GA3 had significantly increased levels of A20 mRNA (4 h) and protein (24 h), resulting in a significant reduction in IL‐6 and IL‐8 release. This effect was mediated via reduced IκBα degradation and reduced NF‐κB (p65) expression. Furthermore, the anti‐inflammatory action of GA3 was abolished in A20‐silenced cells.
Conclusions and Implications
We showed that A20 induction by GA3 attenuates inflammation in airway epithelial cells, at least in part through its effect on NF‐κB and IκBα. GA3 or gibberellin‐derived derivatives could potentially be developed into anti‐inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction.
Linked Articles
This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4
Abdominal aortic aneurysms represent a life-threatening condition characterized by chronic inflammation, destructive remodeling of the extracellular matrix, and increased local expression of matrix ...metalloproteinases (MMPs). Both 92-kD gelatinase (MMP-9) and macrophage elastase (MMP-12) have been implicated in this disease, but it is not known if either is necessary in aneurysmal degeneration. We show here that transient elastase perfusion of the mouse aorta results in delayed aneurysm development that is temporally associated with transmural mononuclear inflammation, increased local production of several elastolytic MMPs, and progressive destruction of the elastic lamellae. Elastase-induced aneurysmal degeneration was suppressed by treatment with a nonselective MMP inhibitor (doxycycline) and by targeted gene disruption of MMP-9, but not by isolated deficiency of MMP-12. Bone marrow transplantation from wild-type mice prevented the aneurysm-resistant phenotype in MMP-9-deficient animals, and wild-type mice acquired aneurysm resistance after transplantation from MMP-9-deficient donors. These results demonstrate that inflammatory cell expression of MMP-9 plays a critical role in an experimental model of aortic aneurysm disease, suggesting that therapeutic strategies targeting MMP-9 may limit the growth of small abdominal aortic aneurysms.
Summary
Context
In observational studies, low serum 25‐hydroxyvitamin D (25‐OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25‐OHD may have ...beneficial effects on insulin resistance or beta‐cell function. Cross‐sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25‐OHD concentration provide conflicting results.
Objective
This study examined the relationship between serum 25‐OHD concentration and insulin resistance in healthy overweight individuals at increased risk of cardiovascular disease, using optimal assessment techniques.
Methods
A total of 92 subjects (mean age 56·0, SD 6·0 years), who were healthy but overweight (mean body mass index 30·9, SD 2·3 kg/m2), underwent assessments of insulin sensitivity (two‐step euglycaemic hyperinsulinaemic clamp, HOMA2‐IR), beta‐cell function (HOMA2%B), serum 25‐OHD concentration and body composition (DEXA).
Results
Mean total 25‐OHD concentration was 32·2, range 21·8–46·6 nmol/l. No association was demonstrated between serum 25‐OHD concentration and insulin resistance.
Conclusions
In this study using optimal assessment techniques to measure 25‐OHD concentration, insulin sensitivity and body composition, there was no association between serum 25‐OHD concentration and insulin resistance in healthy, overweight individuals at high risk of developing cardiovascular disease. This study suggests the documented inverse association between serum 25‐OHD concentration and risk of type 2 DM is not mediated by a relationship between serum 25‐OHD concentration and insulin resistance.
Recent preclinical trials have shown that alginate injections are a promising treatment for ischemic heart disease. Although improvements in heart function and global structure have been reported ...following alginate implants, the underlying structure is poorly understood. Using high resolution ex vivo MRI and DT-MRI of the hearts of normal control swine (n = 8), swine with induced heart failure (n = 5), and swine with heart failure and alginate injection treatment (n = 6), we visualized and quantified the fibre distribution and implant material geometry. Our findings show that the alginate injectates form solid ellipsoids with a retention rate of 68.7% ± 21.3% (mean ± SD) and a sphericity index of 0.37 ± 0.03. These ellipsoidal shapes solidified predominantly at the mid-wall position with an inclination of -4.9° ± 31.4° relative to the local circumferential direction. Overall, the change to left ventricular wall thickness and myofiber orientation was minor and was associated with heart failure and not the presence of injectates. These results show that alginate injectates conform to the pre-existing tissue structure, likely expanding along directions of least resistance as mass is added to the injection sites. The alginate displaces the myocardial tissue predominantly in the longitudinal direction, causing minimal disruption to the surrounding myofiber orientations.
Failed biliary cannulation occurs in up to 10% of patients undergoing ERCP. There is some controversy as to the safety and efficacy of using precut techniques to achieve biliary cannulation in ...difficult cases. To date, no randomized trial has compared the success and complication rates of precut with the rates for persistence when biliary cannulation is difficult. The aim of this study was to compare the success rates and complication rates of precut with the success rates and complication rates of persistence in cases of difficult biliary cannulation.
Patients without prior sphincterotomy who required biliary cannulation were screened. A "difficult biliary cannulation" was arbitrarily defined as failed cannulation after 12 minutes. These patients were then randomized to continue treatment by needle-knife cut over the roof of the papilla or by persistence with a non-wire-guided, single-lumen papillotome. "Primary" success was defined as deep cannulation within 15 minutes of randomization. Primary and final success rates and complication rates within 30 days after ERCP were compared.
Over a 38-month period a total of 642 patients were screened. Patients in whom biliary cannulation was successful within a time period of 12 minutes or less formed the reference group (n = 580). The remainder of the patients were randomly assigned to the "precut" arm (n = 32) or to the "persistence" arm (n = 30). Primary success rates and complication rates were similar in the precut and persistence arms (75% and 4% respectively for the precut arm vs. 73% and 9% for the persistence arm). The final successful cannulation rate in the entire group of 642 patients was 99.5%.
In experienced hands, precut papillotomy and persistence in cannulation are equally effective in cases of difficult cannulation, with a similar complication rate.
Cultured primary epithelial cells are used to examine inflammation in cystic fibrosis (CF). We describe a new human model system using cultured nasal brushings. Nasal brushings were obtained from 16 ...F508del homozygous patients and 11 healthy controls. Cells were resuspended in airway epithelial growth medium and seeded onto collagen-coated flasks and membranes for use in patch-clamp, ion transport, and mediator release assays. Viable cultures were obtained with a 75% success rate from subjects with CF and 100% from control subjects. Amiloride-sensitive epithelial Na channel current of similar size was present in both cell types while forskolin-activated CF transmembrane conductance regulator current was lacking in CF cells. In Ussing chambers, cells from CF patients responded to UTP but not to forskolin. Spontaneous and cytomix-stimulated IL-8 release was similar (stimulated 29,448 ± 9,025 pg/ml; control 16,336 ± 3,308 pg/ml CF; means ± SE). Thus nasal epithelial cells from patients with CF can be grown from nasal brushings and used in electrophysiological and mediator release studies in CF research.
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