3 research outputs found
Keeping the Invisible hand under control? – Arbitrator’s mandate and assisting third parties
Keeping the Invisible hand under control? – Arbitrator’s mandate and assisting third partie
Electric Field Effect on Phospholipid Monolayers at an Aqueous-Organic Liquid-Liquid Interface
The electric potential difference across cell membranes, known as the membrane
potential, plays an important role in the activation of many biological processes. To investigate
the effect of the membrane potential on the molecular ordering of lipids within a biomimetic
membrane, a self-assembled monolayer of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine
(SOPC) lipids at an electrified 1,2-dichloroethane/water interface is studied with X-ray
reflectivity and interfacial tension. Measurements over a range of electric potential differences,
-150 mV to +130 mV, that encompass the range of typical bio-membrane potentials demonstrate
a nearly constant and stable structure whose lipid interfacial density is comparable to that found
in other biomimetic membrane systems. Measurements at higher positive potentials, up to 330
mV, illustrate a monotonic decrease in the lipid interfacial density and accompanying variations
in the interfacial configuration of the lipid. Molecular dynamics simulations, designed to mimic
the experimental conditions, show that the measured changes in lipid configuration are due
primarily to the variation in area per lipid with increasing applied electric field. Rotation of the
SOPC dipole moment by the torque from the applied electric field appears to be negligible,
except at the highest measured potentials. The simulations confirm in atomistic detail the
measured potential-dependent characteristics of SOPC monolayers. Our hybrid study sheds light
on phospholipid monolayer stability under different membrane potentials, which is important for
understanding membrane processes. This study also illustrates the use of X-ray surface scattering
to probe the ordering of surfactant monolayers at an electrified aqueous-organic liquid-liquid
interface
Exome-wide association study of plasma lipids in >300,000 individuals.
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD