Estimates of regional work in the canine left ventricle

Assessment of the magnitude of regional myocardial work requires knowledge of regional fiber stress and fiber shortening. The theoretical development and experimental validation of a method is presented which used values of estimated active and passive fiber stress according to a fluid-fiber model, and measured fiber strain values. This enables the construction of regional stress-strain diagrams, a regional analog of the pressure-volume area model by Suga and co-investigators, which can be linked to regional oxygen consumption. In the left ventricle, either normally or asynchronously activated, the method yields reliable data on strain and active and passive fiber stress. The relation between estimated regional work and myocardial oxygen demand is in quantitative agreement with previously reported relations between global oxygen demand and measured pressure-volume area. During coronary artery occlusion, however, these values were less reliable, which might be due to inaqdequate knowledge of the (passive) material properties of the myocardium.     

Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis in human hepatoma cell line Hep G2

The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake and degradation of¹²⁵I-LDL in a dose-dependent manner. The drug inhibited cholesterol synthesis and esterification without affecting cellular cholesterol content and bile acid synthesis; cholesterol efflux was slightly increased. These results show that the inhibition of cholesterol synthesis together with the enhanced expression of LDL receptors may partially explain the hypocholesterolemic activity of compound AR12456.     

Setting critical nutrient values for ditches using the eutrophication model PCDitch

Critical nutrient loads to prevent duckweed dominance loads in polder ditches were assessed using the eutrophication model PCDitch. In this article the ecological target was set at 50% duckweed coverage. This may be very high for ditches with a nature function, but is not unreasonable for ditches in agricultural areas, with upwelling nutrient rich groundwater, run-off and drainage. Since the change from a ditch with submersed vegetation to duckweed coverage is often a sudden shift, the choice of the amount of duckweed coverage does not influence the calculated loading very much. The main topic of this paper is to present a method to calculate critical loads of nutrients when ecological targets have been set. Sediment type, residence time and water depth influenced the critical loading rates. The calculated critical phosphorus load ranged from 1.8 to 10.2 g P m⁻² year⁻¹, while the calculated critical nitrogen load stretched from 12.1 to 43.8 g N m⁻² year⁻¹. The concentration ranges that were derived from the loading rate were 0.19–0.42 mg P l⁻¹ and 1.3–3.3 mg N l⁻¹. Since PCDitch does not distinguish between Lemna spp. and Azolla spp., no definite conclusions were drawn concerning the effects of nitrogen reduction. In a model situation a pristine ditch was loaded with phosphorus, which resulted into complete duckweed coverage during summer within a few years. When reducing the phosphorus load, it took 10 years before the original situation was reached again. Dredging would accelerate the process of recovery significantly, because the water depth would increase and the phosphorus release from the sediments in summer would decrease. Received September 2003; accepted in revised form February 2005     

Fast Simulation of Mechanical Heterogeneity in the Electrically Asynchronous Heart Using the MultiPatch Module

Cardiac electrical asynchrony occurs as a result of cardiac pacing or conduction disorders such as left bundle-branch block (LBBB). Electrically asynchronous activation causes myocardial contraction heterogeneity that can be detrimental for cardiac function. Computational models provide a tool for understanding pathological consequences of dyssynchronous contraction. Simulations of mechanical dyssynchrony within the heart are typically performed using the finite element method, whose computational intensity may present an obstacle to clinical deployment of patient-specific models. We present an alternative based on the CircAdapt lumped-parameter model of the heart and circulatory system, called the MultiPatch module. Cardiac walls are subdivided into an arbitrary number of patches of homogeneous tissue. Tissue properties and activation time can differ between patches. All patches within a wall share a common wall tension and curvature. Consequently, spatial location within the wall is not required to calculate deformation in a patch. We test the hypothesis that activation time is more important than tissue location for determining mechanical deformation in asynchronous hearts. We perform simulations representing an experimental study of myocardial deformation induced by ventricular pacing, and a patient with LBBB and heart failure using endocardial recordings of electrical activation, wall volumes, and end-diastolic volumes. Direct comparison between simulated and experimental strain patterns shows both qualitative and quantitative agreement between model fibre strain and experimental circumferential strain in terms of shortening and rebound stretch during ejection. Local myofibre strain in the patient simulation shows qualitative agreement with circumferential strain patterns observed in the patient using tagged MRI. We conclude that the MultiPatch module produces realistic regional deformation patterns in the asynchronous heart and that activation time is more important than tissue location within a wall for determining myocardial deformation. The CircAdapt model is therefore capable of fast and realistic simulations of dyssynchronous myocardial deformation embedded within the closed-loop cardiovascular system.     

Biochemical tracers reveal intra-specific differences in the food webs utilized by individual seabirds

Food web structure regulates the pathways and flow rates of energy, nutrients, and contaminants to top predators. Ecologically and physiologically meaningful biochemical tracers provide a means to characterize and quantify these transfers within food webs. In this study, changes in the ratios of stable N isotopes (e.g., δ¹⁵N), fatty acids (FA), and persistent contaminants were used to trace food web pathways utilized by herring gulls (Larus argentatus) breeding along the shores of the St Lawrence River, Canada. Egg δ¹⁵N values varied significantly among years and were used as an indicator of gull trophic position. Temporal trends in egg δ¹⁵N values were related to egg FA profiles. In years when egg δ¹⁵N values were greater, egg FA patterns reflected the consumption of more aquatic prey. Egg δ¹⁵N values were also correlated with annual estimates of prey fish abundance. These results indicated that temporal changes in aquatic prey availability were reflected in the gull diet (as inferred from ecological tracer profiles in gull eggs). Analysis of individual eggs within years confirmed that birds consuming more aquatic prey occupied higher trophic positions. Furthermore, increases in trophic position were associated with increased concentrations of most persistent organic contaminants in eggs. However, levels of highly brominated polybrominated diphenyl ether congeners, e.g, 2,2′,3,3′,4,4′,5,5′,6,6′-decabromoDE (BDE-209), showed a negative relationship with trophic position. These contrasting findings reflected differences among contaminant groups/homologs in terms of their predominant routes of transfer, i.e., aquatic versus terrestrial food webs. High trophic level omnivores, e.g., herring gulls, are common in food webs. By characterizing ecological tracer profiles in such species we can better understand spatial, temporal, and individual differences in pathways of contaminant, energy, and nutrient flow.     

Mapping carcass and meat quality QTL on Sus Scrofa chromosome 2 in commercial finishing pigs

Quantitative trait loci (QTL) affecting carcass and meat quality located on SSC2 were identified using variance component methods. A large number of traits involved in meat and carcass quality was detected in a commercial crossbred population: 1855 pigs sired by 17 boars from a synthetic line, which where homozygous (A/A) for IGF2. Using combined linkage and linkage disequilibrium mapping (LDLA), several QTL significantly affecting loin muscle mass, ham weight and ham muscles (outer ham and knuckle ham) and meat quality traits, such as Minolta-L* and -b*, ultimate pH and Japanese colour score were detected. These results agreed well with previous QTL-studies involving SSC2. Since our study is carried out on crossbreds, different QTL may be segregating in the parental lines. To address this question, we compared models with a single QTL-variance component with models allowing for separate sire and dam QTL-variance components. The same QTL were identified using a single QTL variance component model compared to a model allowing for separate variances with minor differences with respect to QTL location. However, the variance component method made it possible to detect QTL segregating in the paternal line (e.g. HAMB), the maternal lines (e.g. Ham) or in both (e.g. pHu). Combining association and linkage information among haplotypes improved slightly the significance of the QTL compared to an analysis using linkage information only.     

Adverse environmental conditions influence age-related innate immune responsiveness

Background-  

The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions.