West African and Amerindian ancestry and risk of myocardial infarction and metabolic syndrome in the Central Valley population of Costa Rica

Genetic ancestry and environmental factors may contribute to the ethnic differences in risk of coronary heart disease (CHD), metabolic syndrome (MS) or its individual components. The population of the Central Valley of Costa Rica offers a unique opportunity to assess the role of genetic ancestry in these chronic diseases because it derived from the admixture of a relatively small number of founders of Southern European, Amerindian, and West African origin. We aimed to determine whether genetic ancestry is associated with risk of myocardial infarction (MI), MS and its individual components in the Central Valley of Costa Rica. We genotyped 39 ancestral informative markers in cases (n = 1,998) with a first non-fatal acute MI and population-based controls (n = 1,998) matched for age, sex, and area of residence, to estimate individual ancestry proportions. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using conditional (MI) and unconditional (MS and its components) logistic regression adjusting for relevant confounders. Mean individual ancestry proportions in cases and controls were 57.5 versus 57.8% for the Southern European, 38.4 versus 38.3% for the Amerindian and 4.1 versus 3.8% for the West African ancestry. Compared with Southern European ancestry, each 10% increase in West African ancestry was associated with a 29% increase in MI, OR (95% CI) = 1.29 (1.07, 1.56), and with a 30% increase on the risk of hypertension, OR (95% CI) = 1.30 (1.00, 1.70). Each 10% increase in Amerindian ancestry was associated with a 14% increase on the risk of MS, OR (95% CI) = 1.14 (1.00, 1.30), and 20% increase on the risk of impaired fasting glucose, OR (95% CI) = 1.20 (1.01, 1.42). These results show that the high variability of admixture proportions in the Central Valley population offers a unique opportunity to uncover the genetic basis of ethnic differences on the risk of disease.     

Different effects of concentric and eccentric muscle actions on plasma volume

The effects of concentric (CON) and eccentric (ECC) contractions on Delta plasma volume (PV), heart rate (HR), and lactate in responses to protocols in different body positions were investigated. CON or ECC contractions were performed in either a single-exercise (6 sets of 12 repetitions of leg extensions completed at 80% of 12 repetition maximum [12RM] with 3-minute rest periods) or multiexercise (4 sets of 10 repetitions for both CON and ECC trials of bench press, leg extension, military press, and leg curl at 80% of 10RM with 90-second rest periods) protocols. HR and lactate increased significantly for both protocols from pre- to postexercise for CON but not ECC trials. DeltaPV was greater following both CON single-exercise (-11.48 +/- 1.38%) and multiexercise (-4.64 +/- 0.33%) trials vs. ECC single-exercise (-1.62 +/- 1.69%) and multiexercise (-1.26 +/- 1.20) trials. Data demonstrate ECC exercise in response to single and multiexercise protocols at the same absolute workload as CON exercise produces less cardiovascular stress.     

Mean residence time of O horizon carbon along a climatic gradient in Scandinavia estimated by 14C measurements of archived soils

We used two datasets of ¹⁴C analyses of archived soil samples to study carbon turnover in O horizons from spruce dominated old-growth stands on well-drained podzols in Scandinavia. The main data set was obtained from archived samples from the National Forest Soil Inventory in Sweden and represents a climatic gradient in temperature. Composite samples from 1966, 1972, 1983 and 2000 from four different regions in a latitude gradient ranging from 57 to 67°N were analysed for ¹⁴C content. Along this gradient the C stock in the O horizon ranges from 2.1 kg m^?2 in the north to 3.7 kg m^?2 in the southwest. The other data set contains ¹⁴C analyses from 1986, 1987, 1991, 1996 and 2004 from the O horizons in Birkenes, Norway. Mean residence times (MRT) were calculated using a two compartment model, with a litter decomposition compartment using mass loss data from the literature for the three-first years of decomposition and a humus decomposition compartment with a fitted constant turnover rate. We hypothesized that the climatic gradient would result in different C turnover in different parts of the country between northern and southern Sweden. The use of archived soil samples was very valuable for constraining the MRT calculations, which showed that there were differences between the regions. Longest MRT was found in the northernmost region (41 years), with decreasing residence times through the middle (36 years) and central Sweden (28 years), then again increasing in the southwestern region (40 years). The size of the soil organic carbon (SOC) pool in the O horizon was mainly related to differences in litter input and to a lesser degree to MRT. Because N deposition leads both to larger litter input and to longer MRT, we suggest that N deposition contributes significantly to the latitudinal SOC gradient in Scandinavia, with approximately twice as much SOC in the O horizon in the south compared to the north. The data from Birkenes was in good agreement with the Swedish dataset with MRT estimated to 34 years.     

Nonaccidental properties underlie shape recognition in Mammalian and nonmammalian vision

An infinite number of 2D patterns on the retina can correspond to a single 3D object. How do visual systems resolve this ill-posed problem and recognize objects from only a few 2D retinal projections in varied exposure conditions? Theories of object recognition rely on the nonaccidental statistics of edge properties, mainly symmetry, collinearity, curvilinearity, and cotermination. These statistics are determined by the image-formation process (i.e., the 2D retinal projection of a 3D object ); their existence under a range of viewpoints enables viewpoint-invariant recognition. An important question in behavioral biology is whether the visual systems of nonmammalian animals have also evolved biases to utilize nonaccidental statistics . Here, we trained humans and pigeons to recognize four shapes. With the Bubbles technique, we determined which stimulus properties both species used to recognize the shapes. Both humans and pigeons used cotermination, the most diagnostic nonaccidental property of real-world objects, despite evidence from a model computer observer that cotermination was not the most diagnostic pictorial information in this particular task. This result reveals that a nonmammalian visual system that is different anatomically from the human visual system is also biased to recognize objects from nonaccidental statistics.     

Activation of the NLRP3 inflammasome by intracellular poly I:C

Several RNA viruses can be detected by the inflammasome, which promotes IL-1β and IL-18 secretion, but the underlying mechanisms of detection remain unclear. Cytosolic dsRNA is a replication intermediate of many RNA viruses. We show here that transfection of the dsRNA analogue poly I:C activates the NLRP3 inflammasome via a pathway requiring endosomal acidification. This detection is independent of the other poly I:C sensors: TLR3 and MDA5. These results suggest a mechanism by which cytosolic dsRNA produced during viral infection could activate the NLRP3 inflammasome.     

Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster

Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phosphonotripeptide, K-26 at 1.96 Å resolution. The inhibitor binds exclusively in the S₁ and S₂ binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE·K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids.     

New potent and selective polyfluoroalkyl ketone inhibitors of GVIA calcium-independent phospholipase A2

Group VIA calcium-independent phospholipase A₂ (GVIA iPLA₂) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA₂ inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA₂ inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA₂ inhibitor ever reported with a X_I(50) value of 0.0001, and with no significant inhibition against GIVA cPLA₂ or GV sPLA₂. We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA₂, GIVA cPLA₂, and GV sPLA₂.