Genetic Variants and Their Interactions in the Prediction of Increased Pre-Clinical Carotid Atherosclerosis: The Cardiovascular Risk in Young Finns Study

The relative contribution of genetic risk factors to the progression of subclinical atherosclerosis is poorly understood. It is likely that multiple variants are implicated in the development of atherosclerosis, but the subtle genotypic and phenotypic differences are beyond the reach of the conventional case-control designs and the statistical significance testing procedures being used in most association studies. Our objective here was to investigate whether an alternative approach—in which common disorders are treated as quantitative phenotypes that are continuously distributed over a population—can reveal predictive insights into the early atherosclerosis, as assessed using ultrasound imaging-based quantitative measurement of carotid artery intima-media thickness (IMT). Using our population-based follow-up study of atherosclerosis precursors as a basis for sampling subjects with gradually increasing IMT levels, we searched for such subsets of genetic variants and their interactions that are the most predictive of the various risk classes, rather than using exclusively those variants meeting a stringent level of statistical significance. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the variants, and cross-validation was used to assess how well the predictive models will generalize to other subsets of subjects. By means of our predictive modeling framework with machine learning-based SNP selection, we could improve the prediction of the extreme classes of atherosclerosis risk and progression over a 6-year period (average AUC 0.844 and 0.761), compared to that of using conventional cardiovascular risk factors alone (average AUC 0.741 and 0.629), or when combined with the statistically significant variants (average AUC 0.762 and 0.651). The predictive accuracy remained relatively high in an independent validation set of subjects (average decrease of 0.043). These results demonstrate that the modeling framework can utilize the “gray zone” of genetic variation in the classification of subjects with different degrees of risk of developing atherosclerosis.     

Influence of chain length and unsaturation on sphingomyelin bilayers

Sphingomyelins (SMs) are among the most common phospholipid components of plasma membranes, usually constituting a mixture of several molecular species with various fatty acyl chain moieties. In this work, we utilize atomistic molecular dynamics simulations to study the differences in structural and dynamical properties of bilayers comprised of the most common natural SM species. Keeping the sphingosine moiety unchanged, we vary the amide bonded acyl chain from 16 to 24 carbons in length and examine the effect of unsaturation by comparing lipids with saturated and monounsaturated chains. As for structural properties, we find a slight decrease in average area per lipid and a clear linear increase in bilayer thickness with increasing acyl chain length both in saturated and unsaturated systems. Increasing the acyl chain length is found to further the interdigitation across the bilayer center. This is related to the dynamics of SM molecules, as the lateral diffusion rates decrease slightly for an increasing acyl chain length. Interdigitation also plays a role in interleaflet friction, which is stronger for unsaturated chains. The effect of the cis double bond is most significant on the local order parameters and rotation rates of the chains, though unsaturation shows global effects on overall lipid packing and dynamics as well. Regarding hydrogen bonding or properties related to the lipid/water interface region, no significant effects were observed due to varying chain length or unsaturation. The significance of the findings presented is discussed.     

The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality

Background

The occurrence of variations in the spectrum of cardiovascular disease between different regions of the world and ethnic groups have been the subject of great interest. This study report the 24-h variation of myocardial infarction (MI) occurrence in patients recruited from CCU located in Argentina and Uruguay.

Methods

A cohort of 1063 patients admitted to the CCU within 24 h of the onset of symptoms of an acute MI was examined. MI incidence along the day was computed in 1 h-intervals.

Results

A minimal MI incidence between 03:00 and 07:00 h and the occurrence of a first maximum between 08:00 and 12:00 h and a second maximum between 15:00 and 22:00 h were verified. The best fit curve was a 24 h cosinor (acrophase ~ 19:00 h, accounting for 63 % of variance) together with a symmetrical gaussian bell (maximum at ~ 10:00 h, accounting for 37 % of variance). A similar picture was observed for MI frequencies among different excluding subgroups (older or younger than 70 years; with or without previous symptoms; diabetics or non diabetics; Q wave- or non-Q wave-type MI; anterior or inferior MI location). Proportion between cosinor and gaussian probabilities was maintained among most subgroups except for older patients who had more MI at the afternoon and patients with previous symptoms who were equally distributed among the morning and afternoon maxima.

Conclusion

The results support the existence of two maxima (at morning and afternoon hours) in MI incidence in the Argentine and Uruguayan population.     

Size-assortative Schooling in Free-ranging Sticklebacks

Schooling behaviour is known to be advantageous for individual fish in many respects, including both foraging and predator avoidance. It has been repeatedly predicted by theory that to benefit most from schooling, individuals should associate together non-randomly according to their phenotype. Obeying the predictions of theory, several fish species exhibit size-assortative schooling in the laboratory, but unequivocal evidence for size-assorted schools in the wild is largely lacking. To ascertain the existence of size-assorted schools in the wild, we quantified the body-size distribution of individuals in schools of wild threespine stickleback. Gasterosteus aculeatus, a species that is known to readily form size-assorted schools under experimental conditions. Data were collected from 24 separate schools of juvenile fish in late summer 1994. The fish in those wild schools were size-assorted, confirming the previous laboratory findings and, in accordance with current theory, suggesting that the phenotypic characteristics of individuals may be of importance when schools are formed.     

Differential Chloroplast Proteomics of Temperature Adaptation in Apple (Malus x domestica Borkh.) Microshoots

Temperature stress is one of the most common external factors that plants have to adapt to. Accordingly, plants have developed several adaptation mechanisms to deal with temperature stress. Chloroplasts are one of the organelles that are responsible for the sensing of the temperature signal and triggering a response. Here, chloroplasts are purified from low temperature (4° C), control (22° C) and high temperature (30° C) grown Malus x domestica microshoots. The purity of the chloroplast fractions is evaluated by marker proteins, as well as by using in silico subcellular localization predictions. The proteins are digested using filter‐aided sample processing and analyzed using nano‐LC MS/MS. 733 proteins are observed corresponding to published Malus x domestica gene models and 16 chloroplast genome ‐encoded proteins in the chloroplast preparates. In ANOVA, 56 proteins are found to be significantly differentially abundant (p < 0.01) between chloroplasts isolated from plants grown in different conditions. The differentially abundant proteins are involved in protein digestion, cytoskeleton structure, cellular redox state and photosynthesis, or have protective functions. Additionally, a putative chloroplastic aquaporin is observed. Data are available via ProteomeXchange with identifier PXD014212.     

Temperature restraints on energy forestry in Sweden

Temperature sums (TSUM) and growth units (GU) were used as driving variables in the modelling of energy forest production in Sweden. To construct regional maps of forest production for years with good, average and poor weather conditions, it was necessary to deduce formulae of TSUM and GU on a regional basis for a growing season, defined by daily mean temperatures exceeding 5 ÐC. Temperatures north of the 900 day-degrees line are too low for intensive growing of energy forests of willow clones studied so far. With an average production of 10 tonnes dry matter per hectare per year on one million hectares, available for energy farming in the remaining part of Sweden, energy forests could replace about 20% of the Swedish oil import.     

Conformational Changes and Slow Dynamics through Microsecond Polarized Atomistic Molecular Simulation of an Integral Kv1.2 Ion Channel

Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins—not to mention numerous applications in drug design. Here, we present a full 1 µs atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120° rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation (∼35°) of the extracellular end of all S4 segments is present also in a reference 0.5 µs simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 3₁₀ helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4–lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5–1 µs). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations.     

Weed species diversity and community composition in cropping practices at two intensity levels – a six-year experiment

Alternative cropping practices can be expected to increase the diversity and change the species composition of weed communities. In a six-year field experiment we compared species diversity and species composition in the weed community of cereal fields cultivated by conventional and by low-input cropping methods. In the conventional cropping both mineral fertilizers and herbicides were applied but in the low-input cropping the fertlizer was manure and herbicides were avoided altogether. The level of nitrogen fertilization was higher in conventional cropping. A five-year crop rotation comprising rye, oat-pea, barley and two-year grasslands was used in both cropping methods. We found that the species pool was larger (42 vs 35 species) and the average number of species higher (20.2 vs 13.1 species) in low-input than in conventional cropping. This was the case both in the data pooled across crops and in each crop separately. Herbicides affected species diversity and species composition more than did nitrogen fertilization. Species susceptible to the herbicides applied declined in abundance, which resulted in more skewed dominance patterns in the communities of conventional fields than in those of low-input fields. The crop affected the species composition of weed communities more than did the cropping method. Our results suggest that weed species diversity could be promoted by using low-intensity cropping practices.     

Activity traps and the corer: complementary methods for sampling aquatic invertebrates

We compared the picture of aquatic invertebrate fauna given by three types of sampling methods: the corer as well as bottom and mid-water activity traps. The corer mainly caught benthic animals (89%), the most numerous groups of which were chironomids and sphaerids. Nekton was more abundant in activity traps (77% in bottom and 63% in mid-water), the most numerous groups were Cladocera and water mites. The size distributions in catch of the corer and the activity traps differed but there was no difference between the two types of activity traps. In activity traps, individuals of the smallest size class were most abundant, wheras animals of the second smallest size class were most numerous in the corer. We suggest that activity traps and the corer could be used as complementary methods to sample aquatic invertebrate communities.