Concerted transpositions of mobile genetic elements coupled with fitness changes in Drosophila melanogaster

In an inbred low-activity (LA) strain of Drosophila melanogaster with a low level of fitness and a complex of inadaptive characters, in situ hybridization reveals an invariant pattern of distribution of three copia-like elements (mdg-1, mdg-3, and copia). Rare, spontaneous, multiple transpositions of mobile elements in the LA strain were shown to be coupled with a drastic increase of fitness. A changed pattern of various types of mobile elements was also observed on selecting the LA strain for higher fitness. High-fitness strains show transpositions of mobile elements to definite chromosomal sites ("hot spots"). Concerted changes in the location of three different mobile elements were found to be coupled with an increase of fitness. The mdg-1 distribution patterns were also examined in two low-fitness strains independently selected from the high-fitness ones. Fitness decrease was accompanied by mdg-1 excision from the hot spots of their location usually detected in the high-fitness strains. The results suggest the existence of a system of adaptive transpositions of mobile elements that takes part in fitness control.      

Strong coupling of plant and fungal community structure across western Amazonian rainforests

The Amazon basin harbors a diverse ecological community that has a critical role in the maintenance of the biosphere. Although plant and animal communities have received much attention, basic information is lacking for fungal or prokaryotic communities. This is despite the fact that recent ecological studies have suggested a prominent role for interactions with soil fungi in structuring the diversity and abundance of tropical rainforest trees. In this study, we characterize soil fungal communities across three major tropical forest types in the western Amazon basin (terra firme, seasonally flooded and white sand) using 454 pyrosequencing. Using these data, we examine the relationship between fungal diversity and tree species richness, and between fungal community composition and tree species composition, soil environment and spatial proximity. We find that the fungal community in these ecosystems is diverse, with high degrees of spatial variability related to forest type. We also find strong correlations between α- and β-diversity of soil fungi and trees. Both fungal and plant community β-diversity were also correlated with differences in environmental conditions. The correlation between plant and fungal richness was stronger in fungal lineages known for biotrophic strategies (for example, pathogens, mycorrhizas) compared with a lineage known primarily for saprotrophy (yeasts), suggesting that this coupling is, at least in part, due to direct plant–fungal interactions. These data provide a much-needed look at an understudied dimension of the biota in an important ecosystem and supports the hypothesis that fungal communities are involved in the regulation of tropical tree diversity.     

Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion

The strength and spatiotemporal activity of Nodal signaling is tightly controlled in early implantation mouse embryos, including by autoregulation and feedback loops, and involves secreted and intracellular antagonists. These control mechanisms, which are established at the extra-embryonic/embryonic interfaces, are essential for anterior-posterior patterning of the epiblast and correct positioning of the primitive streak. Formation of an ectopic primitive streak, or streak expansion, has previously been reported in mutants lacking antagonists that target Nodal signaling. Here, we demonstrate that loss-of-function of a major bone morphogenetic protein (BMP) effector, Smad5, results in formation of an ectopic primitive streak-like structure in mutant amnion accompanied by ectopic Nodal expression. This suggests that BMP/Smad5 signaling contributes to negative regulation of Nodal. In cultured cells, we find that BMP-activated Smad5 antagonizes Nodal signaling by interfering with the Nodal-Smad2/4-Foxh1 autoregulatory pathway through the formation of an unusual BMP4-induced Smad complex containing Smad2 and Smad5. Quantitative expression analysis supports that ectopic Nodal expression in the Smad5 mutant amnion is induced by the Nodal autoregulatory loop and a slow positive-feedback loop. The latter involves BMP4 signaling and also induction of ectopic Wnt3. Ectopic activation of these Nodal feedback loops in the Smad5 mutant amnion results in the eventual formation of an ectopic primitive streak-like structure. We conclude that antagonism of Nodal signaling by BMP/Smad5 signaling prevents primitive streak formation in the amnion of normal mouse embryos.     

Randomly and Non-Randomly Missing Renal Function Data in the Strong Heart Study: A Comparison of Imputation Methods

Kidney and cardiovascular disease are widespread among populations with high prevalence of diabetes, such as American Indians participating in the Strong Heart Study (SHS). Studying these conditions simultaneously in longitudinal studies is challenging, because the morbidity and mortality associated with these diseases result in missing data, and these data are likely not missing at random. When such data are merely excluded, study findings may be compromised. In this article, a subset of 2264 participants with complete renal function data from Strong Heart Exams 1 (1989–1991), 2 (1993–1995), and 3 (1998–1999) was used to examine the performance of five methods used to impute missing data: listwise deletion, mean of serial measures, adjacent value, multiple imputation, and pattern-mixture. Three missing at random models and one non-missing at random model were used to compare the performance of the imputation techniques on randomly and non-randomly missing data. The pattern-mixture method was found to perform best for imputing renal function data that were not missing at random. Determining whether data are missing at random or not can help in choosing the imputation method that will provide the most accurate results.     

The post-infarction nurse practitioner project

Objectives To confirm the feasibility of nurse practitioner interventionin non-high-risk patients with recent myocardial infarction (MI). Design Observational study. Setting Acute coronary care unit in a teaching hospital. Methods We performed an open-label feasibility study to identify non-high-risk MI patients and evaluate the outcome of a new nurse practitioner intervention programme. The initial pilot phase served to identify the non-high-risk population. In the subsequent confirmation phase, 500 consecutive non-high-risk post-MI patients with preserved LV function without heart failure were included to receive nurse practitioner management. The nurse practitioner intervention started on transfer from the coronary care unit to the cardiology ward and continued thereafter for up to 30 days. Main outcome measures Time to first event analysis of death from all causes or repeat myocardial infarction. Results 500 Patients without signs of heart failure or depressed LV function were identified as nonhigh- risk and eligible for inclusion in the nurse practitioner intervention programme. In the implementation phase, none of the patients died and 0.9% developed a repeat myocardial infarction after 30 days of follow-up. Compared with the pilot phase, patients in the implementation phase spent fewer days in hospital (mean 11.1 versus 6.2 days; p<0.001). Conclusion It is feasible to identify non-high-risk post-MI patients, who can be managed adequately by a nurse practitioner. Embedding experienced nurse practitioners within critical care pathways may result in significant decreases in length of hospital stay. (Neth Heart J 2009;17:61-7.)     

In search of an efficient strategy to monitor disease status of chronic heart failure outpatients: added value of blood biomarkers to clinical assessment

Introduction

Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed.

Methods

Between 2011–2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured N?terminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and C?reactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time-dependent Cox models were used.

Results

Mean age was 67 ± 13 years, 72% were men and 27% were in NYHA class III–IV. We obtained 886 repeated measures (median 3 [IQR 2–5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6–1.4] year. Repeatedly measured NT-proBNP and Hs-TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: β [95% CI]: 1.56 [1.17–2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: β [95% CI]: 1.58 [1.21–2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73–4.73]), CRP (1.69 [1.21–2.34]) and NYHA class (2.33 [1.51–3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82.

Conclusion

Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients.

     

Emergency cardiac surgery after a failed percutaneous coronary intervention in an interventional centre without on-site cardiac surgery

Background. Based on experience from other countries, the Medical Centre Alkmaar was granted permission to start the first Dutch PCI programme without on-site cardiac surgery. The cardiology group of the Medical Centre Alkmaar started an off-site PCI programme in 2002 with only primary PCI in the first year and a full PCI programme from November 2003 onwards. We report the first Dutch experience with acute cardiac surgery following a failed PCI procedure in an off-site clinic. Patients. From October 2002 until February 2007, 2500 patients were treated by PCI in the Medical Centre Alkmaar. These patients were treated for an acute myocardial infarction (33%), acute coronary syndromes (37%) or progressive angina (30%). In this first series of off-site PCI in the Netherlands, the incidence of emergency cardiac surgery following failed PCI was 0.2% All five patients who needed emergency surgery underwent elective PCI for progressive stable coronary artery disease. No emergency surgery was needed for primary PCIs in patients with an acute myocardial infarction. All patients survived emergency surgery following failed PCI. Conclusion. Adherence to the Dutch guidelines of interventional cardiology with protocols describing a close collaboration with cardiac surgeons and an immediate availability of rapid ground transportation are mandatory when performing off-site PCI. This series extends the current expertise of emergency surgery after failed PCI to off-site clinics. With appropriate settings, off-site PCI may not be associated with an increase in the risk of adverse events. (Neth Heart J 2007;15:173-7.)