Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment in vitro

Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge. Airway smooth muscle cells (ASMCs) are the major effector cells of bronchoconstriction in asthma and also contribute to the inflammatory process by secreting pro-inflammatory cytokines and chemokines. Therefore, ASMCs are a major target of both β2-agonist and ICS treatment [3]. Although several studies have suggested that steroid signalling [4] or β2-adrenoceptor (β2AR) signalling may be abnormally regulated in severe asthma [5], it remains unknown whether impaired airway smooth muscle corticosteroid and/or β2-agonist response may contribute to the development of FAO. The aim of this study was to investigate whether primary human ASMCs obtained from severe asthma patients with FAO differ in their response to β2-agonists and corticosteroids compared with asthma patients without FAO and healthy controls. We hypothesised that ASMCs from asthma patients with FAO are less responsive to corticosteroid and β2-agonist treatment than those from patients without FA

Black Stork Down: Military Discourses in Bird Conservation in Malta

Tensions between Maltese hunters and bird conservation NGOs have intensified over the past decade. Conservation NGOs have become frustrated with the Maltese State for conceding to the hunter lobby and negotiating derogations from the European Union’s Bird Directive. Some NGOs have recently started to organize complex field-operations where volunteers are trained to patrol the landscape, operate drones and other surveillance technologies, detect illegalities, and lead police teams to arrest poachers. We describe the sophisticated military metaphors which conservation NGOs have developed to describe, guide and legitimize their efforts to the Maltese public and their fee-paying members. We also discuss why such groups might be inclined to adopt these metaphors. Finally, we suggest that anthropological studies of discourse could help understand delicate contexts such as this where conservation NGOs, hunting associations and the State have ended in political deadlock

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Understanding the Sequence-Dependence of DNA Groove Dimensions: Implications for DNA Interactions

BACKGROUND: The B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. It has long been thought that the groove dimensions depend on the DNA sequence, however this relationship has remained elusive. Here, our aim is to elucidate how the DNA sequence intrinsically shapes the grooves. METHODOLOGY/PRINCIPAL FINDINGS: The present study is based on the analysis of datasets of free and protein-bound DNA crystal structures, and from a compilation of NMR (31)P chemical shifts measured on free DNA in solution on a broad range of representative sequences. The (31)P chemical shifts can be interpreted in terms of the BI↔BII backbone conformations and dynamics. The grooves width and depth of free and protein-bound DNA are found to be clearly related to the BI/BII backbone conformational states. The DNA propensity to undergo BI↔BII backbone transitions is highly sequence-dependent and can be quantified at the dinucleotide level. This dual relationship, between DNA sequence and backbone behavior on one hand, and backbone behavior and groove dimensions on the other hand, allows to decipher the link between DNA sequence and groove dimensions. It also firmly establishes that proteins take advantage of the intrinsic DNA groove properties. CONCLUSIONS/SIGNIFICANCE: The study provides a general framework explaining how the DNA sequence shapes the groove dimensions in free and protein-bound DNA, with far-reaching implications for DNA-protein indirect readout in both specific and non specific interactions

Targeted emission reductions from global super-polluting power plant units

There are more than 30,000 biomass- and fossil-fuel-burning power plants now operating worldwide, reflecting a tremendously diverse infrastructure, which ranges in capacity from less than a megawatt to more than a gigawatt. In 2010, 68.7% of electricity generated globally came from these power plants, compared with 64.2% in 1990. Although the electricity generated by this infrastructure is vital to economic activity worldwide, it also produces more CO2 and air pollutant emissions than infrastructure from any other industrial sector. Here, we assess fuel- and region-specific opportunities for reducing undesirable air pollutant emissions using a newly developed emission dataset at the level of individual generating units. For example, we find that retiring or installing emission control technologies on units representing 0.8% of the global coal-fired power plant capacity could reduce levels of PM2.5 emissions by 7.7–14.2%. In India and China, retiring coal-fired plants representing 1.8% and 0.8% of total capacity can reduce total PM2.5 emissions from coal-fired plants by 13.2% and 16.0%, respectively. Our results therefore suggest that policies targeting a relatively small number of ‘super-polluting’ units could substantially reduce pollutant emissions and thus the related impacts on both human health and global climate

Averaged Differential Expression for the Discovery of Biomarkers in the Blood of Patients with Prostate Cancer

<div><h3>Background</h3><p>The identification of a blood-based diagnostic marker is a goal in many areas of medicine, including the early diagnosis of prostate cancer. We describe the use of averaged differential display as an efficient mechanism for biomarker discovery in whole blood RNA. The process of averaging reduces the problem of clinical heterogeneity while simultaneously minimizing sample handling.</p> <h3>Methodology/Principal Findings</h3><p>RNA was isolated from the blood of prostate cancer patients and healthy controls. Samples were pooled and subjected to the averaged differential display process. Transcripts present at different levels between patients and controls were purified and sequenced for identification. Transcript levels in the blood of prostate cancer patients and controls were verified by quantitative RT-PCR. Means were compared using a t-test and a receiver-operating curve was generated. The Ring finger protein 19A (RNF19A) transcript was identified as having higher levels in prostate cancer patients compared to healthy men through the averaged differential display process. Quantitative RT-PCR analysis confirmed a more than 2-fold higher level of RNF19A mRNA levels in the blood of patients with prostate cancer than in healthy controls (p = 0.0066). The accuracy of distinguishing cancer patients from healthy men using RNF19A mRNA levels in blood as determined by the area under the receiving operator curve was 0.727.</p> <h3>Conclusions/Significance</h3><p>Averaged differential display offers a simplified approach for the comprehensive screening of body fluids, such as blood, to identify biomarkers in patients with prostate cancer. Furthermore, this proof-of-concept study warrants further analysis of RNF19A as a clinically relevant biomarker for prostate cancer detection.</p> </div