Browning reduces the availability—but not the transfer—of essential fatty acids in temperate lakes

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Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy

Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered ¹H NMR spectroscopy. Our method uses diffusion coefficients to provide a direct measure of the mean particle sizes and numbers. Using 177 plasma samples from healthy individuals and the concentration of ApoB and ApoA from isolated lipoprotein fractions, our test showed a stronger correlation between the NMR-derived lipoprotein particle numbers and apolipoprotein concentrations than the LipoProfile^® test commercialized by Liposcience. We also converted LDL particle numbers to ApoB equivalents (milligrams per deciliter) and our test yielded similar values of LDL-ApoB to the LipoProfile^® test (absolute mean bias of 8.5 and 7.4 mg/dl, respectively). In addition, our HDL particle number values were more concordant with the calibrated values determined recently using ion mobility. Finally, principal component analysis distinguished type 2 diabetic patients with and without atherogenic dyslipidemia (AD) on a second cohort of 307 subjects characterized using the Liposcale test (area under the curve = 0.88) and showed concordant relationships between variables explaining AD. Altogether, our method provides reproducible and reliable characterization of lipoprotein particles and it is applicable to pathological states such as AD.     

Widespread Signals of Convergent Adaptation to High Altitude in Asia and America

Living at high altitude is one of the most difficult challenges that humans had to cope with during their evolution. Whereas several genomic studies have revealed some of the genetic bases of adaptations in Tibetan, Andean, and Ethiopian populations, relatively little evidence of convergent evolution to altitude in different continents has accumulated. This lack of evidence can be due to truly different evolutionary responses, but it can also be due to the low power of former studies that have mainly focused on populations from a single geographical region or performed separate analyses on multiple pairs of populations to avoid problems linked to shared histories between some populations. We introduce here a hierarchical Bayesian method to detect local adaptation that can deal with complex demographic histories. Our method can identify selection occurring at different scales, as well as convergent adaptation in different regions. We apply our approach to the analysis of a large SNP data set from low- and high-altitude human populations from America and Asia. The simultaneous analysis of these two geographic areas allows us to identify several candidate genome regions for altitudinal selection, and we show that convergent evolution among continents has been quite common. In addition to identifying several genes and biological processes involved in high-altitude adaptation, we identify two specific biological pathways that could have evolved in both continents to counter toxic effects induced by hypoxia.     

The YmdB Phosphodiesterase Is a Global Regulator of Late Adaptive Responses in Bacillus subtilis

Bacillus subtilis mutants lacking ymdB are unable to form biofilms, exhibit a strong overexpression of the flagellin gene hag, and are deficient in SlrR, a SinR antagonist. Here, we report the functional and structural characterization of YmdB, and we find that YmdB is a phosphodiesterase with activity against 2′,3′- and 3′,5′-cyclic nucleotide monophosphates. The structure of YmdB reveals that the enzyme adopts a conserved phosphodiesterase fold with a binuclear metal center. Mutagenesis of a catalytically crucial residue demonstrates that the enzymatic activity of YmdB is essential for biofilm formation. The deletion of ymdB affects the expression of more than 800 genes; the levels of the σ^D-dependent motility regulon and several sporulation genes are increased, and the levels of the SinR-repressed biofilm genes are decreased, confirming the role of YmdB in regulating late adaptive responses of B. subtilis.     

Acidification Asymmetrically Affects Voltage-dependent Anion Channel Implicating the Involvement of Salt Bridges

The voltage-dependent anion channel (VDAC) is the major pathway for ATP, ADP, and other respiratory substrates through the mitochondrial outer membrane, constituting a crucial point of mitochondrial metabolism regulation. VDAC is characterized by its ability to “gate” between an open and several “closed” states under applied voltage. In the early stages of tumorigenesis or during ischemia, partial or total absence of oxygen supply to cells results in cytosolic acidification. Motivated by these facts, we investigated the effects of pH variations on VDAC gating properties. We reconstituted VDAC into planar lipid membranes and found that acidification reversibly increases its voltage-dependent gating. Furthermore, both VDAC anion selectivity and single channel conductance increased with acidification, in agreement with the titration of the negatively charged VDAC residues at low pH values. Analysis of the pH dependences of the gating and open channel parameters yielded similar pK_a values close to 4.0. We also found that the response of VDAC gating to acidification was highly asymmetric. The presumably cytosolic (cis) side of the channel was the most sensitive to acidification, whereas the mitochondrial intermembrane space (trans) side barely responded to pH changes. Molecular dynamic simulations suggested that stable salt bridges at the cis side, which are susceptible to disruption upon acidification, contribute to this asymmetry. The pronounced sensitivity of the cis side to pH variations found here in vitro might provide helpful insights into the regulatory role of VDAC in the protective effect of cytosolic acidification during ischemia in vivo.     

Environmental significance of gypsum-bearing layers at the “Lo Hueco” paleontological site (Upper Cretaceous,Cuenca, Spain): petrography,fluid inclusions,and isotopic relations

“Lo Hueco” (Cuenca, Spain) is an upper Campanian–lower Maastrichtian Fossil-Lagerstätte that has provided more than 8,500 well-preserved macrofossils, including titanosaur sauropod dinosaurs. Although the facies and fossil record point to both fresh and brackish or marine water influences, a detailed study of the sulphate-bearing layers of the site through petrography, fluid inclusions, and isotopes has been undertaken to evaluate the possible marine influence. The two main sulphate units of the “Lo Hueco” site consist chiefly of bimodal micro- to meso- lenticular gypsum crystals that grew displacively in a clayey-carbonate sediment. The well-preserved lenticular gypsum crystals are primary, as demonstrated by the presence of the original twinning and the absence of hydration textures or anhydrite relicts. Primary fluid inclusions of the lenticular gypsum crystals indicate a vadose environment of formation, with salinities between 1,800 and 14,000 ppm, pointing to a brackish but non-marine environment. Furthermore, gypsum exhibits ⁸⁷Sr/⁸⁶Sr values between 0.708034 and 0.708120, which are higher than those from marine evaporites of Campanian–Maastrichtian age, indicating a clear influence of fresh water. Gypsum δ ³⁴S _VCDT values (18.1 to 19.0 ± 0.5 ‰) and δ ¹⁸O_VSMOW values (11.0 to 15.2 ± 0.5 ‰), on the other hand, are typical isotopic values recorded in marine evaporites of this age. This apparent contradiction between fluid inclusion and Sr isotopic data is probably the result of some recycling from Upper Cretaceous evaporites. Based on all these observations, the sulphate-bearing layers are interpreted as probably formed in a near-coastal saline mudflat of a playa lake. As a whole, this study highlights the importance of combining different proxies when dealing with evaporites formed in brackish-water environments.     

Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population

The aim of the present study was to establish the gene frequency of six polymorphisms of the ABCB1, CYP3A5, CYP2C19, and P2RY12 genes in a population resident of Mexico City. The proteins encoded by these genes have been associated with the absorption, and biotransformation of clopidogrel. The ABCB1 T3435C, CYP3A5 V3* A6986G, P2RY12 G52T, P2RY12 C34T, CYP2C19 V2* and V3* (positions G681A and G636A, respectively), polymorphisms were analyzed by 5′ exonuclease TaqMan genotyping assays in a group of 269 healthy unrelated Mexican Mestizo individuals. The CYP2C19 V3* G636A polymorphism was not detected in the Mexican Mestizos population. However, the studied population presented significant differences (P < 0.05) in the distribution of the T3435C, A6986G, G681A, G52T and C34T polymorphisms when compared to reported frequencies of Amerindian of South America, Caucasian, Asian, and African populations. In summary, the distribution of the ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms distinguishes to the Mexican Mestizos population from other ethnic groups.