Loss of phylogenetic information in chorion gene families of Bombyx mori gene conversion

The silkmoth chorion has provided a stimulating model for the study of evolution and developmental regulation of gene families. Previous attempts at inferring relationships among chorion sequences have been based on pairwise comparisons of overall similarity, a potentially problematic approach. To remedy this, we identified the alignable regions of low sequence variability and then analyzed this restricted database by parsimony and neighbor-joining methods. At the deepest level, the chorion sequence tree is split into two branches, called "alpha" and "beta." Within each branch, early- and late-expressing genes each constitute monophyletic groups, while the situation with middle-expressing genes remains uncertain. The HcB gene family appears to be the most basal beta-branch group, but this conclusion is qualified because the effect of gene conversion on branching order is unknown. Previous studies by Eickbush and colleagues have strongly suggested that ErA, HcA, and HcB families undergo gene conversion within a gene family, whereas the ErB family does not. The occurrence of conversion correlates with a particular tree structure; namely, branch lengths are much greater at the base of the family than at higher internodes and terminal branches. These observations raise the possibility that chorion gene families are defined by gene conversion events (reticulate evolution) rather than by descent with modification (synapomorphy).      

First record of a spiral form of Aulacoseira,A. ambigua f. japonica (F.Meister) Tuji & D.M.Williams,in South African fresh waters

Water quality and algal populations in the Vaal River Barrage Reservoir have been monitored extensively for many decades, because of its importance as a water source for the most densely populated area in South Africa. Although Aulacoseira granulata (Ehrenberg) Simonsen is frequently found and at it times dominates algal assemblages in the Barrage, Aulacoseira ambigua (F.Meister) Tuji & D.M.Williams has never before been recorded at this locality. During a countrywide proficiency-testing scheme for algae counting, coordinated by Rand Water, spiral-shaped diatom colonies with distinctly curved cells were detected during May 2015. Upon investigation, it was found that the spiral colonies were Aulacoseira ambigua f. japonica, its presence in the fresh waters of South Africa being recorded for the first time. Since their first appearance during May 2015, colonies of Aulacoseira ambigua f. japonica have been constantly present in the surface waters of the Barrage. Their presence at this site can be linked to increasing eutrophication in the Vaal River, because the spiral form is known to prefer eutrophic conditions. Centric diatoms rarely form spiral colonies and there is some confusion in the literature as to the identity of this particular form, therefore in this paper we discuss this taxon, its nomenclature and ecological significance.     

Actualités sur les dosages de parathormone : des difficultés analytiques à l’interprétation des résultats en clinique

Parathyroid hormone (PTH) is an 84-amino acid peptide hormone that is measured with difficulties. Firstly, the blood sample is currently performed on serum or EDTA plasma. The interassay variability according to the method requires the use of serum. Secondly, specificity depends on the method. The PTH intact assays were thought to bind only 1–84 PTH. At the present time, it is well-known that these assays cross-react with PTH fragments including 7–84 PTH. Third-generation assays without cross-reaction have been recently developed. At the present time, these assays have not shown any superior value than the second-generation assays in the treatment of renal osteodystrophy for which cut-off values of 150 and 300 ng/L have been reported by the K/DOKI. These values can be maintained if the method gives results similar to those obtained with the Allegro assay that was the reference method for K/DOKI recommendations. By contrast, we propose to use assay-specific decision limits for patients or to apply a correcting factor to the PTH values for the methods giving different results with the Allegro assay. Further recommendations from expert groups working for harmonization of different PTH tests should be considered.     

T lymphocyte insensitivity to corticosteroids in chronic obstructive pulmonary disease

Background

There are increased numbers of activated lymphocytes in the lungs of chronic obstructive pulmonary disease (COPD) patients. The clinical benefits of corticosteroids in COPD patients are limited. Our hypothesis is that lymphocytes play a role in this corticosteroid insensitivity.

Objectives

To investigate the effects of the corticosteroid dexamethasone on lung lymphocyte cytokine production from patients with COPD compared to controls.

Methods

Cultured airway lymphocytes obtained by bronchoscopy from healthy non-smokers (HNS), smokers (S) and COPD patients were stimulated with phytohaemagglutinin (PHA) & phorbol myristate acetate (PMA), +/- dexamethasone. Supernatants were assayed for interleukin (IL)-2 and interferon (IFN)γ. Immunofluoresence was used to analyse changes in CD8 glucocorticoid receptor (GRα and GRβ) expression.

Results

The inhibition of PHA/PMA stimulated IFNγ production by dexamethasone was reduced in COPD patients compared to HNS (p < 0.05 at concentrations from 0.1-1 μM). There was also a significant reduction (p < 0.05) in the mean inhibitory effect at 1 μM in COPD patients (54.1%) compared to smokers (72.1%), and in smokers compared to HNS (85.5%). There was a numerically reduced effect of dexamethasone on IL-2 production that did not reach statistical significance. There was no difference in GRα and GRβ expression in follicular CD8 cells between COPD patients (50.9% and 30.4% respectively) and smokers (52.9% and 29.7% respectively).

Conclusions

IFNγ production from COPD airway lymphocytes is corticosteroid insensitive. This phenomenon may be important in the poor clinical response often observed with corticosteroids.     

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

Background  

Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism.     

Use of spatiotemporal analysis of laboratory submission data to identify potential outbreaks of new or emerging diseases in cattle in Great Britain

Background  

New and emerging diseases of livestock may impact animal welfare, trade and public health. Early detection of outbreaks can reduce the impact of these diseases by triggering control measures that limit the number of cases that occur. The aim of this study was to investigate whether prospective spatiotemporal methods could be used to identify outbreaks of new and emerging diseases in scanning surveillance data. SaTScan was used to identify clusters of unusually high levels of submissions where a diagnosis could not be reached (DNR) using different probability models and baselines. The clusters detected were subjected to a further selection process to reduce the number of false positives and a more detailed epidemiological analysis to ascertain whether they were likely to represent real outbreaks.     

Withdrawal of inhaled corticosteroids in individuals with COPD - a systematic review and comment on trial methodology

Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn. Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies. Data extraction was completed independently by two reviewers. The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration. We included four trials; the quality of three was adequate. In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant. Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice. There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes. Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication. In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly. Intention to treat analyses should be used and interpreted appropriately.     

Degree of methylation of ZAC1 (PLAGL1) is associated with prenatal and post-natal growth in healthy infants of the EDEN mother child cohort

The ZAC1 gene, mapped to the 6q24 region, is part of a network of co-regulated imprinted genes involved in the control of embryonic growth. Loss of methylation at the ZAC1 differentially methylated region (DMR) is associated with transient neonatal diabetes mellitus, a developmental disorder involving growth retardation and diabetes in the first weeks of post-natal life. We assessed whether the degree of methylation of the ZAC1 DMR in leukocytes DNA extracted from cord blood is associated with fetal, birth and post-natal anthropometric measures or with C-peptide concentrations in cord serum. We also searched for an influence of dietary intake and maternal parameters on ZAC1 DMR methylation. We found positive correlations between the ZAC1 DMR methylation index (MI) and estimated fetal weight (EFW) at 32 weeks of gestation, weight at birth and weight at one year of age (respectively, r = 0.15, 0.09, 0.14; P values = 0.01, 0.15, 0.03). However, there were no significant correlations between the ZAC1 DMR MI and cord blood C-peptide levels. Maternal intakes of alcohol and of vitamins B2 were positively correlated with ZAC1 DMR methylation (respectively, r = 0.2 and 0.14; P = 0.004 and 0.04). The influence of ZAC1 seems to start in the second half of pregnancy and continue at least until the first year of life. The maternal environment also appears to contribute to the regulation of DNA methylation.     

Defining adult asthma endotypes by clinical features and patterns of volatile organic compounds in exhaled air

Background

Several classifications of adult asthma patients using cluster analyses based on clinical and demographic information has resulted in clinical phenotypic clusters that do not address molecular mechanisms. Volatile organic compounds (VOC) in exhaled air are released during inflammation in response to oxidative stress as a result of activated leukocytes. VOC profiles in exhaled air could distinguish between asthma patients and healthy subjects. In this study, we aimed to classify new asthma endotypes by combining inflammatory mechanisms investigated by VOC profiles in exhaled air and clinical information of asthma patients.

Methods

Breath samples were analyzed for VOC profiles by gas chromatography–mass spectrometry from asthma patients (n = 195) and healthy controls (n = 40). A total of 945 determined compounds were subjected to discriminant analysis to find those that could discriminate healthy from asthmatic subjects. 2-step cluster analysis based on clinical information and VOCs in exhaled air were used to form asthma endotypes.

Results

We identified 16 VOCs, which could distinguish between healthy and asthma subjects with a sensitivity of 100% and a specificity of 91.1%. Cluster analysis based on VOCs in exhaled air and the clinical parameters FEV1, FEV1 change after 3 weeks of hospitalization, allergic sensitization, Junipers symptoms score and asthma medications resulted in the formation of 7 different asthma endotype clusters. We identified asthma clusters with different VOC profiles but similar clinical characteristics and endotypes with similar VOC profiles, but distinct clinical characteristics.

Conclusion

This study demonstrates that both, clinical presentation of asthma and inflammatory mechanisms in the airways should be considered for classification of asthma subtypes.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0136-8) contains supplementary material, which is available to authorized users.