Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by altering the structure and function of pulmonary vessels at early disease stages. The objectives of this study were to evaluate the effects of long-term exposure to cigarette smoke on endothelial function and smooth muscle-cell proliferation in pulmonary arteries of guinea pigs.</p> <p>Methods</p> <p>19 male Hartley guinea pigs were exposed to the smoke of 7 cigarettes/day, 5 days/week, for 3 and 6 months. 17 control guinea pigs were sham-exposed for the same periods. Endothelial function was evaluated in rings of pulmonary artery and aorta as the relaxation induced by ADP. The proliferation of smooth muscle cells and their phenotype in small pulmonary vessels were evaluated by immunohistochemical expression of α-actin and desmin. Vessel wall thickness, arteriolar muscularization and emphysema were assessed morphometrically. The expression of endothelial nitric oxide synthase (eNOS) was evaluated by Real Time-PCR.</p> <p>Results</p> <p>Exposure to cigarette smoke reduced endothelium-dependent vasodilatation in pulmonary arteries (ANOVA p < 0.05) but not in the aorta. Endothelial dysfunction was apparent at 3 months of exposure and did not increase further after 6 months of exposure. Smoke-exposed animals showed proliferation of poorly differentiated smooth muscle cells in small vessels (p < 0.05) after 3 months of exposure. Prolonged exposure resulted in full muscularization of small pulmonary vessels (p < 0.05), wall thickening (p < 0.01) and increased contractility of the main pulmonary artery (p < 0.05), and enlargement of the alveolar spaces. Lung expression of eNOS was decreased in animals exposed to cigarette smoke.</p> <p>Conclusion</p> <p>In the guinea pig, exposure to cigarette smoke induces selective endothelial dysfunction in pulmonary arteries, smooth muscle cell proliferation in small pulmonary vessels and reduced lung expression of eNOS. These changes appear after 3 months of exposure and precede the development of pulmonary emphysema.</p

Oilseed rape (Brassica napus) as a resource for farmland insect pollinators: quantifying floral traits in conventional varieties and breeding systems

This is the final version of the article. Available from the publisher via the DOI in this record.Oilseed rape (OSR; Brassica napus L.) is a major crop in temperate regions and provides an important source ofnutrition to many of the yield-enhancing insect flower visitors that consume floral nectar. The manipulation ofmechanisms that control various crop plant traits for the benefit of pollinators has been suggested in the bid toincrease food security, but little is known about inherent floral trait expression in contemporary OSR varieties orthe breeding systems used in OSR breeding programmes. We studied a range of floral traits in glasshouse-grown, certified conventional varieties of winter OSR to test for variation among and within breeding systems.We measured 24-h nectar secretion rate, amount, concentration and ratio of nectar sugars per flower, and sizesand number of flowers produced per plant from 24 varieties of OSR representing open-pollinated (OP), genicmale sterility (GMS) hybrid and cytoplasmic male sterility (CMS) hybrid breeding systems. Sugar concentrationwas consistent among and within the breeding systems; however, GMS hybrids produced more nectar and moresugar per flower than CMS hybrid or OP varieties. With the exception of ratio of fructose/glucose in OP vari-eties, we found that nectar traits were consistent within all the breeding systems. When scaled, GMS hybridsproduced 1.73 times more nectar resource per plant than OP varieties. Nectar production and amount of nectarsugar in OSR plants were independent of number and size of flowers. Our data show that floral traits of glass-house-grown OSR differed among breeding systems, suggesting that manipulation and enhancement of nectarrewards for insect flower visitors, including pollinators, could be included in future OSR breeding programmes.This work was fundedby the BBSRC, including support from an Insect Pollinators Ini-tiative grant awarded to GAW (BB/I000968/1) that was jointlyfunded by the BBSRC, NERC, the Wellcome Trust, Defra, andthe Scottish Government. Support was also received from HighWycombe Beekeepers’ Association. Rothamsted Researchreceives strategic funding from the Biotechnology and BiologicalSciences Research Council (BBSRC) of the UK

Exploiting Chordality in Optimization Algorithms for Model Predictive Control

In this chapter we show that chordal structure can be used to devise efficient optimization methods for many common model predictive control problems. The chordal structure is used both for computing search directions efficiently as well as for distributing all the other computations in an interior-point method for solving the problem. The chordal structure can stem both from the sequential nature of the problem as well as from distributed formulations of the problem related to scenario trees or other formulations. The framework enables efficient parallel computations.Comment: arXiv admin note: text overlap with arXiv:1502.0638

ACADEMIC DISCIPLINE «ALTERNATIVE ENERGY»: A TUTORIAL ASPECT

The necessity to update academic discipline contents taking into account international experience is shown. At the School of Ecology in the framework of British Council project «Alternative Energy: Education and Science» (implemented together with Keele University, UK) the course «Alternative Energy» was updated: new topics were included, new methods of teaching were introduced. The content of the course is presented in details. Due to up-dating students receive new competencies which allow them to solve complex problems and to be more competitive on the labour market

Microtubules regulate cardiomyocyte transversal Young's modulus.

The field of cardiomyocyte mechanobiology is gaining significant attention, due to accumulating evidence concerning the significant role of cellular mechanical effects on the integrated function of the heart. To date, the protein titin has been demonstrated as a major contributor to the cardiomyocytes Young's modulus (YM). The microtubular network represents another potential regulator of cardiac mechanics. However, the contribution of microtubules (MTs) to the membrane YM is still understudied and has not been interrogated in the context of myocardial infarction (MI) or mechanical loading and unloading. Using nanoscale mechanoscanning ion conductance microscopy, we demonstrate that MTs contribute to cardiomyocyte transverse YM in healthy and pathological states with different mechanical loading. Specifically, we show that posttranslational modifications of MTs have differing effects on cardiomyocyte YM: Acetylation provides flexibility, whereas detyrosination imparts rigidity. Further studies demonstrate that there is no correlation between the total protein amount of acetylated and detyrosinated MT. Yet, in the polymerized-only populations, an increased level of acetylation results in a decline of detyrosinated MTs in an MI model

KiDS-1000 catalogue: Redshift distributions and their calibration

We present redshift distribution estimates of galaxies selected from the fourth data release of the Kilo-Degree Survey over an area of ∼1000 deg2 (KiDS-1000). These redshift distributions represent one of the crucial ingredients for weak gravitational lensing measurements with the KiDS-1000 data. The primary estimate is based on deep spectroscopic reference catalogues that are re-weighted with the help of a self-organising map (SOM) to closely resemble the KiDS-1000 sources, split into five tomographic redshift bins in the photometric redshift range 0.1 < zB ≤ 1.2. Sources are selected such that they only occupy that volume of nine-dimensional magnitude-space that is also covered by the reference samples (‘gold’ selection). Residual biases in the mean redshifts determined from this calibration are estimated from mock catalogues to be ≲0.01 for all five bins with uncertainties of ∼0.01. This primary SOM estimate of the KiDS-1000 redshift distributions is complemented with an independent clustering redshift approach. After validation of the clustering-z on the same mock catalogues and a careful assessment of systematic errors, we find no significant bias of the SOM redshift distributions with respect to the clustering-z measurements. The SOM redshift distributions re-calibrated by the clustering-z represent an alternative calibration of the redshift distributions with only slightly larger uncertainties in the mean redshifts of ∼0.01 − 0.02 to be used in KiDS-1000 cosmological weak lensing analyses. As this includes the SOM uncertainty, clustering-z are shown to be fully competitive on KiDS-1000 data

Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD.

Long-term, low-dose azithromycin reduces exacerbation frequency in chronic obstructive pulmonary disease (COPD), yet the mechanism remains unclear. This study characterised genome-wide gene expression changes in patients with neutrophilic COPD following long-term, low-dose azithromycin treatment. Patients with neutrophilic COPD (>61% or >162×104 cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database. In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p1.5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p1.3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses. Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients

Factors associated with variability in the assessment of UK doctors' professionalism: analysis of survey results.

OBJECTIVES: To investigate potential sources of systematic bias arising in the assessment of doctors' professionalism. DESIGN: Linear regression modelling of cross sectional questionnaire survey data. SETTING: 11 clinical practices in England and Wales. PARTICIPANTS: 1065 non-training grade doctors from various clinical specialties and settings, 17,031 of their colleagues, and 30,333 of their patients. MAIN OUTCOME MEASURES: Two measures of a doctor's professional performance using patient and colleague questionnaires from the United Kingdom's General Medical Council (GMC). We selected potential predictor variables from the characteristics of the doctors and of their patient and colleague assessors. RESULTS: After we adjusted for characteristics of the doctor as well as characteristics of the patient sample, less favourable scores from patient feedback were independently predicted by doctors having obtained their primary medical degree from any non-European country; doctors practising as a psychiatrist; lower proportions of white patients providing feedback; lower proportions of patients rating their consultation as being very important; and lower proportions of patients reporting that they were seeing their usual doctor. Lower scores from colleague feedback were independently predicted by doctors having obtained their primary medical degree from countries outside the UK and South Asia; currently employed in a locum capacity; working as a general practitioner or psychiatrist; being employed in a staff grade, associate specialist, or other equivalent role; and with a lower proportion of colleagues reporting they had daily or weekly professional contact with the doctor. In fully adjusted models, the doctor's age, sex, and ethnic group were not independent predictors of patient or colleague feedback. Neither the age or sex profiles of the patient or colleague samples were independent predictors of doctors' feedback scores, and nor was the ethnic group of colleague samples. CONCLUSIONS: Caution is necessary when considering patient and colleague feedback regarding doctors' professionalism. Multisource feedback undertaken for revalidation using the GMC patient and colleague questionnaires should, at least initially, be principally formative in nature

Insights Into Aboriginal Australian Mortuary Practices: Perspectives From Ancient DNA

Paleogenetics is a relatively new and promising field that has the potential to provide new information about past Indigenous social systems, including insights into the complexity of burial practices. We present results of the first ancient DNA (aDNA) investigation into traditional mortuary practices among Australian Aboriginal people with a focus on North-East Australia. We recovered mitochondrial and Y chromosome sequences from five ancestral Aboriginal Australian remains that were excavated from the Flinders Island group in Cape York, Queensland. Two of these individuals were sampled from disturbed beach burials, while the other three were from bundle burials located in rock shelters. Genomic analyses showed that individuals from all three rock shelter burials and one of the two beach burials had a close genealogical relationship to contemporary individuals from communities from Cape York. In contrast the remaining male individual, found buried on the beach, had a mitochondrial DNA sequence that suggested that he was not from this location but that he was closely related to people from central Queensland or New South Wales. In addition, this individual was associated with a distinctive burial practice to the other four people. It has been suggested that traditionally non-locals or lower status individuals were buried on beaches. Our findings suggest that theories put forward about beach burials being non-local, or less esteemed members of the community, can potentially be resolved through analyses of uniparental genomic data. Generally, these results support the suggestion often derived from ethnohistoric accounts that inequality in Indigenous Australian mortuary practices might be based on the status, sex, and/or age of individuals and may instead relate to place of geographic origin. There is, however, some departure from the traditional ethnohistoric account in that complex mortuary internments were also offered to female individuals of the community, with genomic analyses helping to confirm that the gender of one of the rockshelter internments was that of a young female

Brain metastasis from urachal carcinoma: the importance of locally aggressive treatment

We present the case of a 52 years old woman who developed multiple brain metastasis after cystectomy with anterior exenteration and chemotherapy. She received whole-brain radiotherapy with 20 gray in 5 sessions. On magnetic resonance imaging 8 weeks after radiotherapy she showed a regression of some lesions while others responded only partially. This case-report and a review of the literature show the importance of aggressive local treatment in patients with brain metastasis from urachal carcinoma