Dietary and circulating long-chain omega-3 polyunsaturated fatty acids and mortality risk after myocardial infarction:A long-term follow-up of the alpha omega cohort

BACKGROUND: Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. METHODS AND RESULTS: We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52– 0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86– 0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53–1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53– 0.94] for >2.52% versus ≤1.29%; 0.85 [0.77– 0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. CONCLUSIONS: In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03192410

Cardiomyocyte hypocontractility and reduced myofibril density in end-stage pediatric cardiomyopathy

Dilated cardiomyopathy amongst children (pediatric cardiomyopathy, pediatric CM) is associated with a high morbidity and mortality. Because little is known about the pathophysiology of pediatric CM, treatment is largely based on adult heart failure therapy. The reason for high morbidity and mortality is largely unknown as well as data on cellular pathomechanisms is limited. Here, we assessed cardiomyocyte contractility and protein expression to define cellular pathomechanisms in pediatric CM. Explanted heart tissue of 11 pediatric CM patients and 18 controls was studied. Contractility was measured in single membrane-permeabilized cardiomyocytes and protein expression was assessed with gel electrophoresis and western blot analysis. We observed increased Ca2+-sensitivity of myofilaments which was due to hypophosphorylation of cardiac troponin I, a feature commonly observed in adult DCM. We also found a significantly reduced maximal force generating capacity of pediatric CM cardiomyocytes, as well as a reduced passive force development over a range of sarcomere lengths. Myofibril density was reduced in pediatric CM compared to controls. Correction of maximal force and passive force for myofibril density normalized forces in pediatric CM cardiomyocytes to control values. This implies that the hypocontractility was caused by the reduction in myofibril density. Unlike in adult DCM we did not find an increase in compliant titin isoform expression in end-stage pediatric CM. The limited ability of pediatric CM patients to maintain myofibril density might have contributed to their early disease onset and severity

Reduced tillage, but not organic matter input, increased nematode diversity and food web stability in European long‐term field experiments

Soil nematode communities and food web indices can inform about the complexity, nutrient flows and decomposition pathways of soil food webs, reflecting soil quality. Relative abundance of nematode feeding and life‐history groups are used for calculating food web indices, i.e., maturity index (MI), enrichment index (EI), structure index (SI) and channel index (CI). Molecular methods to study nematode communities potentially offer advantages compared to traditional methods in terms of resolution, throughput, cost and time. In spite of such advantages, molecular data have not often been adopted so far to assess the effects of soil management on nematode communities and to calculate these food web indices. Here, we used high‐throughput amplicon sequencing to investigate the effects of tillage (conventional vs. reduced) and organic matter addition (low vs. high) on nematode communities and food web indices in 10 European long‐term field experiments and we assessed the relationship between nematode communities and soil parameters. We found that nematode communities were more strongly affected by tillage than by organic matter addition. Compared to conventional tillage, reduced tillage increased nematode diversity (23% higher Shannon diversity index), nematode community stability (12% higher MI), structure (24% higher SI), and the fungal decomposition channel (59% higher CI), and also the number of herbivorous nematodes (70% higher). Total and labile organic carbon, available K and microbial parameters explained nematode community structure. Our findings show that nematode communities are sensitive indicators of soil quality and that molecular profiling of nematode communities has the potential to reveal the effects of soil management on soil quality

Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment.

OBJECTIVES: To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. DESIGN: An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls. METHODS: Plasma marker ('analyte') levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression. RESULTS: Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands. CONCLUSIONS: Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection

Comparison of Zn_{1-x}Mn_xTe/ZnTe multiple-quantum wells and quantum dots by below-bandgap photomodulated reflectivity

Large-area high density patterns of quantum dots with a diameter of 200 nm have been prepared from a series of four Zn_{0.93}Mn_{0.07}Te/ZnTe multiple quantum well structures of different well width (4 nm, 6 nm, 8 nm and 10 nm) by electron beam lithography followed by Ar+ ion beam etching. Below-bandgap photomodulated reflectivity spectra of the quantum dot samples and the parent heterostructures were then recorded at 10 K and the spectra were fitted to extract the linewidths and the energy positions of the excitonic transitions in each sample. The fitted results are compared to calculations of the transition energies in which the different strain states in the samples are taken into account. We show that the main effect of the nanofabrication process is a change in the strain state of the quantum dot samples compared to the parent heterostructures. The quantum dot pillars turn out to be freestanding, whereas the heterostructures are in a good approximation strained to the ZnTe lattice constant. The lateral size of the dots is such that extra confinement effects are not expected or observed.Comment: 23 pages, LaTeX2e (amsmath, epsfig), 7 EPS figure

Conformational Mechanics of Polymer Adsorption Transitions at Attractive Substrates

Conformational phases of a semiflexible off-lattice homopolymer model near an attractive substrate are investigated by means of multicanonical computer simulations. In our polymer-substrate model, nonbonded pairs of monomers as well as monomers and the substrate interact via attractive van der Waals forces. To characterize conformational phases of this hybrid system, we analyze thermal fluctuations of energetic and structural quantities, as well as adequate docking parameters. Introducing a solvent parameter related to the strength of the surface attraction, we construct and discuss the solubility-temperature phase diagram. Apart from the main phases of adsorbed and desorbed conformations, we identify several other phase transitions such as the freezing transition between energy-dominated crystalline low-temperature structures and globular entropy-dominated conformations.Comment: 13 pages, 15 figure

Voronoia: analyzing packing in protein structures

The packing of protein atoms is an indicator for their stability and functionality, and applied in determining thermostability, in protein design, ligand binding and to identify flexible regions in proteins. Here, we present Voronoia, a database of atomic-scale packing data for protein 3D structures. It is based on an improved Voronoi Cell algorithm using hyperboloid interfaces to construct atomic volumes, and to resolve solvent-accessible and -inaccessible regions of atoms. The database contains atomic volumes, local packing densities and interior cavities calculated for 61 318 biological units from the PDB. A report for each structure summarizes the packing by residue and atom types, and lists the environment of interior cavities. The packing data are compared to a nonredundant set of structures from SCOP superfamilies. Both packing densities and cavities can be visualized in the 3D structures by the Jmol plugin. Additionally, PDB files can be submitted to the Voronoia server for calculation. This service performs calculations for most full-atomic protein structures within a few minutes. For batch jobs, a standalone version of the program with an optional PyMOL plugin is available for download. The database can be freely accessed at: http://bioinformatics.charite.de/voronoia