Saturated Chains Research Articles

Oxidation of Unsaturated Phospholipids: A Monolayer Study.

Lipid oxidation does strongly influence the self-organization of plasma membranes; the detailed influence is not yet clear. In this work, phospholipid monolayers at the air/water interface were used as model membranes. Oxidation was induced by the reactive oxygen species formed in a H2O2-enriched solution. The reaction was found to be diffusion-limited; the concentration of the reactive oxygen species was about 50 nM. Isotherms were recorded for different phosphatidylcholines with saturated and unsaturated acyl chains. For unsaturated lipids, the isotherms showed a constant relative molecular area increase after oxidization, independent of the molecular area and dependent on the degree of peroxidation. Similarly, the compressibility modulus was unchanged, but shifted to larger molecular areas. The correlation between peroxidation and changes of the interaction forces between the lipid molecules is discussed.

Binding of warfarin differently affects the thermal behavior and chain packing of anionic, zwitterionic and cationic lipid membranes

Warfarin is a coumarin derivative drug widely used for its anticoagulant properties. The interaction of warfarin with fully hydrated lipid bilayers has been studied by combining differential scanning calorimetry, spectrophotometry, electron spin resonance of chain-labelled lipids and molecular docking. Bilayers formed by lipids with different chemico-physical properties were considered, namely dimyristoyl-phosphatidylcholine (DMPC), dimyristoyl-phosphatidylglycerol (DMPG), and dioleoyltrimethyl-ammoniumpropane (DOTAP). We observed in all cases the binding of warfarin in proximity of the surface of the bilayers, leading to a variety of distinct effects on key molecular properties of the membranes. The drug associates with the lipid bilayers in the deprotonated open chain form, with an association constant similar for DMPC and DMPG (1.27·104 and 2.82·104 M−1, respectively) and lower for DOTAP (0.46·104 M−1). In DMPC bilayers, which are zwitterionic and with saturated symmetrical chains, warfarin at 10 mol% suppresses the pre-transition, slightly stabilizes the fluid state and reduces the cooperativity of the main transition. Moreover, it alters the lateral packing density of the chain segments close to the polar/apolar interface at any temperature through the gel phase. In anionic DMPG bilayers, the drug slightly perturbs the thermotropic phase behavior, and at 10 mol% markedly loosens the compact gel phase packing of the first chain segments. In cationic DOTAP bilayers, possessing unsaturated acyl chains, the drug induces a slightly higher degree of order and motional restriction in the outer hydrocarbon region in the frozen state. In all cases, as a surface adsorbed molecule, warfarin does not affect the segmental chain order and dynamics for temperatures in the fluid phase. The overall results provide an outline of the action of warfarin on membranes formed by lipids of different types.

The hepatic lipidome and HNF4α and SHBG expression in human liver.

Low plasma levels of sex hormone-binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-CoA desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids, while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but the expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined. The relationship of all FA studied to HNFα and SHBG mRNAs was inverse, and similar to that for total triglyceride concentrations, irrespective of chain length and saturation vs unsaturation.

Electron scattering processes in steroid molecules via NEGF-DFT: The opening of conduction channels by central oxygen

We present a careful analysis of the electron transport in a variety of steroid derivatives attached among Au (111) electrodes. Our discussion is based on the non-equilibrium Green’s function formalism coupled to the density functional theory, as well as appropriate parameters, such as the current-voltage behavior, differential conductance, rectification ratio, transmittance, the projected density of states, and the corresponding eigenchannels. The systems investigated present antagonistic features. While the cholesterol has no appreciable electrical rectification and works as an insulator, cortisol presents an evident diode-like behavior with an intense micro-ampere current with a strong peak at ca. 0.3 eV. This characteristic is a consequence of the systematic remotion of saturated carbon chains, and the inclusion of oxygen atoms. These results can help to understand biological processes involving these molecules besides designing new devices for applications in molecular electronics.

Thermodynamic quantification of sodium dodecyl sulfate penetration in cholesterol and phospholipid monolayers

Sodium dodecyl sulfate (SDS) is one of the extensively used surfactants in bioprocesses. Present work analyzes the penetration of SDS in pure and mixed Langmuir monolayers consisting of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. A series of isotherms are obtained by compressing the monolayers over subphase containing varying concentrations of SDS. The extent of penetration of SDS is quantified in terms of its mole percentage in the monolayer by applying various thermodynamic equations derived from Gibbs adsorption equation. Analysis of pure monolayers shows that SDS penetration is directly correlated with the monolayer fluidity and the lipid packing density. We find that POPC monolayers, which do not pack closely on compression due to a kink in one of the acyl chains, exhibit higher SDS penetration than DPPC monolayers which are more rigid due to two saturated acyl chains that pack very efficiently. The SDS penetration is also analyzed in mixed lipid monolayers in which the lipids are present in molar proportions similar to that in the plasma membranes of mammalian cells. Thermodynamic quantification shows that mixed monolayers of DPPC with POPC (in 2:1 molar ratio) exhibit penetration similar to pure POPC monolayers indicating dominating effect of unsaturated phospholipids on membrane packing. We find lower SDS penetration in mixed cholesterol-POPC monolayers than pure POPC monolayers at all surface pressures and for all SDS subphase concentrations used. This confirms with the well-known condensation effect of cholesterol on POPC monolayers. Cholesterol is known to have a rigidifying effect on DPPC monolayers at low surface pressures and a fluidizing effect at high surface pressures. Consistent with these experimental observations, our thermodynamic quantification predicts lower SDS penetration at low pressures and higher penetration at high pressures when compared to pure DPPC monolayers. Thus, thermodynamic theories are able to accurately predict the experimentally observed trends for penetration in mixed monolayers of cholesterol with POPC and DPPC. Our work demonstrates that thermodynamic quantification is a reliable technique to estimate extent of penetration of various additives in pure and mixed lipid monolayers.

A composition based approach to predict density, viscosity and surface tension of biodiesel fuels

The variations in biodiesel composition based on the feedstock used for its production result in significant variations in the fuel properties and thereby, engine characteristics. This necessitates the need for adopting a composition based approach to analyze biodiesel fuel properties and engine characteristics. Based on this premise, biodiesel composition based multi linear regression models are proposed in the present work to predict the density, kinematic viscosity and surface tension of biodiesel. Biodiesel composition effects are captured through two new parameters, namely straight chain saturation factor (SCSF) and modified degree of unsaturation (DUm) which represents the effects of saturated and unsaturated methyl ester constituents of biodiesel, respectively. SCSF and DUm are found to better capture the effects of biodiesel composition as compared to the parameters available in the literature, namely long chain saturated factor, modified long chain saturated factor and degree of unsaturation by addressing their limitations. The proposed models also account for the effects of temperature on the variations of biodiesel properties. To train and validate the proposed multi linear regression models, the density and kinematic viscosity in the temperature range of 293 to 373 K and surface tension in the temperature range of 303 to 353 K of seven biodiesels having significantly different composition are measured. For validation, the measured property data of three additional biodiesels not considered in training the models are used. The predictions compared well with measured data with regression coefficients of 0.98, 0.97 and 0.93 and mean absolute percentage error of 6.28, 0.36 and 1.4 percent for kinematic viscosity, density and surface tension, respectively. Statistical analysis carried out using ANOVA revealed a strong correlation between biodiesel composition based parameters, SCSF and DUm and aforementioned properties. Further, DUm is found to have a profound influence on the kinematic viscosity and density of biodiesel as compared to SCSF while its effects on the surface tension are statistically insignificant.

Label-free CARS microscopy reveals similar triacylglycerol acyl chain length and saturation in myocellular lipid droplets of athletes and individuals with type 2 diabetes

Aims/hypothesisIntramyocellular lipid (IMCL) content associates with development of insulin resistance, albeit not in insulin-sensitive endurance-trained athletes (trained). Qualitative and spatial differences in muscle lipid composition may underlie this so-called athlete’s paradox. Here we studied triacylglycerol (TAG) composition of individual myocellular lipid droplets (LDs) in trained individuals and individuals with type 2 diabetes mellitus.MethodsTrained ( dot{V}{mathrm{O}}_{2max } 71.0 ± 1.6 ml O2 [kg lean body mass (LBM)]−1 min−1), normoglycaemic (fasting glucose 5.1 ± 0.1 mmol/l) individuals and untrained ( dot{V}{mathrm{O}}_{2max } 36.8 ± 1.5 ml O2 [kg LBM]−1 min−1) individuals with type 2 diabetes (fasting glucose 7.4 ± 0.5 mmol/l), with similar IMCL content (3.5 ± 0.7% vs 2.5 ± 0.3%, p = 0.241), but at opposite ends of the insulin sensitivity spectrum (glucose infusion rate 93.8 ± 6.6 vs 25.7 ± 5.3 μmol [kg LBM]−1 min−1 for trained individuals and those with type 2 diabetes, respectively) were included from our database in the present study. We applied in situ label-free broadband coherent anti-Stokes Raman scattering (CARS) microscopy to sections from skeletal muscle biopsies to measure TAG acyl chain length and saturation of myocellular LDs. This approach uniquely permits examination of individual LDs in their native environment, in a fibre-type-specific manner, taking into account LD size and subcellular location.ResultsDespite a significant difference in insulin sensitivity, we observed remarkably similar acyl chain length and saturation in trained and type 2 diabetic individuals (chain length: 18.12 ± 0.61 vs 18.36 ± 0.43 number of carbons; saturation: 0.37 ± 0.05 vs 0.38 ± 0.06 number of C=C bonds). Longer acyl chains or higher saturation (lower C=C number) could be detected in subpopulations of LDs, i.e. large LDs (chain length: 18.11 ± 0.48 vs 18.63 ± 0.57 carbon number) and subsarcolemmal LDs (saturation: 0.34 ± 0.02 vs 0.36 ± 0.04 C=C number), which are more abundant in individuals with type 2 diabetes.Conclusions/interpretationIn contrast to reports of profound differences in the lipid composition of lipids extracted from skeletal muscle from trained and type 2 diabetic individuals, our in situ, LD-specific approach detected only modest differences in TAG composition in LD subpopulations, which were dependent on LD size and subcellular location. If, and to what extent, these modest differences can impact insulin sensitivity remains to be elucidated.Graphical abstract

Dual-mode global stabilization of high-order saturated integrator chains: LMI-based MPC combined with a nested saturated feedback

This paper considers the problem of high-performance global stabilization of an integrator chain via a bounded control at the presence of input disturbance. While nested saturated feedback (NSF) is known as the most inspiring existing solution in the literature, we shall highlight the inherent shortcomings of this approach which cause a poor performance in terms of convergence rate. Then, a novel dual-mode control scheme combining an improved NSF law with a linear matrix inequality (LMI)-based model predictive controller (MPC) is developed to overcome the weaknesses of pure NSF. By offline calculations, a set of nested robust invariant attraction regions and their attributed feedback gains are computed respecting the known bound for disturbance. In online implementation, an improved NSF law is adopted (as the first mode) to bring states within the largest invariant set. The proposed LMI-based state feedback law is applied thereafter (as the second mode) to bring state vector toward the origin with a fast convergence rate. In both modes, the well-known extended state observer (ESO) is employed to effectively suppress the external disturbance. The superiority of the proposed globally stabilizing scheme in terms of faster convergence and improved disturbance rejection ability is demonstrated comparing performances of foremost existing solutions in case of a triple integrator chain.

Supramolecular organization of α-galactosylceramide in pure dispersions and in cationic DODAB bilayers

α-galactosylceramide (α-GalCer; KRN7000) strongly stimulates NKT cells. The structures of α-GalCer assemblies and of cationic DODAB bilayers containing α-GalCer were investigated by differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy. Assemblies of α-GalCer have a very tightly packed gel phase, causing spin labels to cluster and display spin exchange interactions. An endothermic phase transition is observed by DSC, leading to a fluid phase. This phase transition peak disappears upon mixing with DODAB, showing that up to 9 mol% α-GalCer is miscible with the cationic lipid. ESR spectra show that α-GalCer decreases DODAB gel phase packing, resulting in a decrease of gel-fluid transition temperature and cooperativity in DSC thermograms of mixed bilayers. In contrast, α-GalCer increases the rigidity of the fluid phase. These effects are probably due to the conformation of the rigid amide bond that connects the phytosphingosine base of α-GalCer to its long and saturated acyl chain. Possibly, α-GalCer adopts a V-shaped conformation because of the perpendicular orientation of the amide bond towards the axes of the hydrocarbon chains. Apparently, the effect of the amide bond configuration is a key structural feature for the interaction between ceramide-based glycolipids and DODAB molecules, since we have previously reported a similar decrease of gel phase packing and increase in fluid phase rigidity for DODAB bilayers containing C24:1β-glucosylceramide. Since the structure of delivery systems is critical to the biological activity of α-GalCer, this work certainly contributes to the planning and development of novel immunotherapeutic tools.

The Disordering Effect of Plant Metabolites on Model Lipid Membranes of Various Thickness

This study was focused on the effect of plant metabolites (phloretin, capsaicin, digitonin, diosgenin and betulin) on the model lipid membranes. The methods of assessing the permeability of lipid bilayers based on measuring the leakage of a fluorescent marker (calcein) from liposomes and differential scanning microcalorimetry of vesicle suspension were used. It was found that the release rate of calcein from 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) liposomes with test compounds added to the suspension at a ratio with lipid 1 : 50 decreased in the order capsaicin > phloretin >> betulin ≈ diosgenin ≈ digitonin. In the case of cholesterol- and ergosterol-containing POPC liposomes, the activity decreased as diosgenin ≈ digitonin > betulin > capsaicin > phloretin. It was demonstrated that phloretin and capsaicin significantly reduce the melting temperature (Tm) and to increase the half-width of the main peak on the endotherm (T1/2) of dipalmitoylphosphocholine (DPPC), distearoylphosphocholine (DSPC) and diarachidoylphosphocholine (DAPC). These results show that the incorporation of these small molecules between the polar “heads” of phosphocholine. It was found that the increase in the length of saturated chains of membrane-forming lipids (from 16 to 20 hydrocarbon units), the absolute values of ΔTm and ΔT1/2 decreased in the presence of phloretin and increased with capsaicin. This may be the result of differences in the localization of phloretin and capsaicin in the membrane. Steroid saponins exhibited a weak effect on the thermotropic behavior of phosphocholines. The absolute values of ΔTm and ΔT1/2 decreased in the order DPPC, DSPC, and DAPC and increased in the order betulin, diosgenin, and digitonin. Steroid saponins are characterized by a more pronounced effect on the thermotropic behavior of the sterol–phospholipid mixture. The findings are consistent with the assumption of a high affinity of the tested saponins for sterol-containing membranes.

Oleaginous potential of indigenously isolated fresh water microalgae for biofuel production

ABSTRACT Fresh water samples from six perennial rain fed reservoirs were collected for isolation of microalgae by enrichment method. Eighteen isolates belonging to cyanophyta and chlorophyta were obtained after 15 days of incubation in BG-11 medium under 16: 8 light and dark cycle at room temperature. Upon evaluation of oleaginous potential for future application in biodiesel synthesis, only three isolates BV3 (Nostoc sp.), BV4 (Nostoc sp.) and BV14 (Cyanobacteria) were selected. Lipid production, growth profile and lipid characteristic were also studied for the three isolates. The lipid content of the isolates BV 3, BV4 and BV14 were found to be 12.306 ± 1.313, 17.309 ± 2.129 and 26.567 ± 3.582% DW, respectively and lipid productivity recorded were 0.159 ± 0.011, 0.106 ± 0.007 and 0.046 ± 0.004 g L−1d−1, respectively. The specific growth rate was also determined for BV3 (0.177 d−1), BV4 (0.233 d−1) and BV14 (0.183 d−1). Analysis of lipid further revealed the presence of neutral lipids and saturated short chain alkanes.

Corrosion inhibitor by a polymerizable columnar mesogen based on hexabenzocoronene derivative

AbstractA hexa‐peri‐hexabenzocoronene derivative (HBC‐1,2,4‐Ph‐DA‐C12) with the central HBC core tethered with three diacetylene (DA)‐containing chains and three saturated alkyl chains was applied for the anticorrosion of an iron surface. This compound, which exhibits a columnar liquid crystalline phase, could be polymerized by ultraviolet irradiation through reactions between the DA units. This polymer coating exhibited a good anticorrosion property with good hydrophobicity (contact angle [CA] ~ 84°–105°) and excellent mechanical property. It showed a high resistance of 149 kΩ/cm2, much higher than that of known anticorrosion materials.

Novel mannopyranoside esters as sterol 14α-demethylase inhibitors: Synthesis, PASS predication, molecular docking, and pharmacokinetic studies

Direct unimolar one-step valeroylation of methyl α-d-mannopyranoside (MDM) furnished mainly 6-O-valeroate. However, similar reaction catalyzed by DMAP resulted 3,6-di-O-valeroate (21%) and 6-O-valeroate (47%) indicating reactivity sequence as 6-OH>3-OH>2-OH,4-OH. To get potential antimicrobial agents, 6-O-valeroate was converted into four 2,3,4-di-O-acyl esters, and 3,6-di-O-valeroate was converted into 2,4-di-O-acetate. Direct tetra-O-valeroylation of MDM gave a mixture of 2,3,4,6-tetra-O-valeroate and 2,3,6-tri-O-valeroate indicating that the C2–OH is more reactive than the equatorial C4–OH. The activity spectra analysis along with in vitro antimicrobial evaluation clearly indicated that these novel MDM esters had better antifungal activities over antibacterial agents. In this connection, molecular docking indicated that these MDM esters acted as competitive inhibitors of sterol 14α-demethylase (CYP51), an essential enzyme for clinical target to cure several infectious diseases. Furthermore, pharmacokinetic studies revealed that these MDM esters may be worth considering as potent candidates for oral and topical administration. Structure activity relationship (SAR) affirmed that saturated valeric chain (C5) in combination with caprylic (C8) chains was more promising CYP51 inhibitor over conventional antifungal antibiotics.

Elucidating How Different Amphipathic Stabilizers Affect BSA Protein Conformational Properties and Adsorption Behavior.

Natural proteins such as bovine serum albumin (BSA) are readily extracted from biological fluids and widely used in various applications such as drug delivery and surface coatings. It is standard practice to dope BSA proteins with an amphipathic stabilizer, most commonly fatty acids, during purification steps to maintain BSA conformational properties. There have been extensive studies investigating how fatty acids and related amphiphiles affect solution-phase BSA conformational properties, while it is far less understood how amphipathic stabilizers might influence noncovalent BSA adsorption onto solid supports, which is practically relevant to form surface coatings. Herein, we systematically investigated the binding interactions between BSA proteins and different molar ratios of caprylic acid (CA), monocaprylin (MC), and methyl caprylate (ME) amphiphiles-all of which have 8-carbon-long, saturated hydrocarbon chains with distinct headgroups-and resulting effects on BSA adsorption behavior on silica surfaces. Our findings revealed that anionic CA had the greatest binding affinity to BSA, which translated into greater solution-phase conformational stability and reduced adsorption-related conformational changes along with relatively low packing densities in fabricated BSA adlayers. On the other hand, nonionic MC had moderate binding affinity to BSA and could stabilize BSA conformational properties in the solution and adsorbed states while also enabling BSA adlayers to form with higher packing densities. We discuss physicochemical factors that contribute to these performance differences, and our findings demonstrate how rational selection of amphiphile type and amount can enable control over BSA adlayer properties, which could lead to improved BSA protein-based surface coatings.

Cooking fat types alter the inherent glycaemic response of niche rice varieties through resistant starch (RS) formation

Studies over the decades highlighted the role of lipids in modulating inherent glycaemic response of rice, still much needed to elucidate how the chain length and saturation of fatty acid (FA) influence this. Hence in this study, we investigated the in vitro glycaemic response, starch-lipid complexing ability and resistant starch (RS) formation in three rice types [white rice (WR), black rice (BR) and red rice (RR)] cooked with four fats [ghee, coconut oil (CO), virgin coconut oil (VCO) and rice bran oil (RBO)], with three cooking conditions (‘before’, ‘during’ and ‘after’). Inherent glycaemic response was found least in RR (81.9%) and among the fats used, RBO rich in long chain unsaturated FA (72.6%) further reduced the least glycaemic response with maximum complexing ability and enriched RS content. Cooking conditions also resulted significant variation in the parameters studied, the most significant effect with complexing ability (28.67%) and RS (2.26%) observed when RBO added ‘during’ with RR. FTIR fingerprint within 950 to 1200 cm−1 region validated the complex interactions of amylose among FA, alcohols and acids present in the RBO. This is the first report proposing a ‘lipid induced resistance towards glycaemic response’ model highlighting the importance of FA type towards modulating the molecular configuration, complexing ability and RS-V formation.

Perfluorocarbons in Chemical Biology.

Perfluorocarbons, saturated carbon chains in which all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds are not found in living systems, they can be used to modify biomolecules to confer orthogonal behavior within natural systems, such as improved stability, engineered assembly, and cell-permeability. Perfluorinated groups also provide handles for purification, mass spectrometry, and 19 F NMR studies in complex environments. Herein, we describe how the unique properties of perfluorocarbons have been employed to understand and manipulate biological systems.

A Quantitative Analysis of Cellular Lipid Compositions During Acute Proteotoxic ER Stress Reveals Specificity in the Production of Asymmetric Lipids.

The unfolded protein response (UPR) is central to endoplasmic reticulum (ER) homeostasis by controlling its size and protein folding capacity. When activated by unfolded proteins in the ER-lumen or aberrant lipid compositions, the UPR adjusts the expression of hundreds of target genes to counteract ER stress. The proteotoxic drugs dithiothreitol (DTT) and tunicamycin (TM) are commonly used to induce misfolding of proteins in the ER and to study the UPR. However, their potential impact on the cellular lipid composition has never been systematically addressed. Here, we report the quantitative, cellular lipid composition of Saccharomyces cerevisiae during acute, proteotoxic stress in both rich and synthetic media. We show that DTT causes rapid remodeling of the lipidome when used in rich medium at growth-inhibitory concentrations, while TM has only a marginal impact on the lipidome under our conditions of cultivation. We formulate recommendations on how to study UPR activation by proteotoxic stress without interferences from a perturbed lipid metabolism. Furthermore, our data suggest an intricate connection between the cellular growth rate, the abundance of the ER, and the metabolism of fatty acids. We show that Saccharomyces cerevisiae can produce asymmetric lipids with two saturated fatty acyl chains differing substantially in length. These observations indicate that the pairing of saturated fatty acyl chains is tightly controlled and suggest an evolutionary conservation of asymmetric lipids and their biosynthetic machineries.

A conserved evolutionary mechanism permits Δ9 desaturation of very-long-chain fatty acyl lipids

Δ9 fatty acyl desaturases introduce a cis-double bond between C9 and C10 of saturated fatty acyl chains. From the crystal structure of the mouse stearoyl-CoA desaturase (mSCD1) it was proposed that Tyr-104, a surface residue located at the distal end of the fatty acyl binding pocket plays a key role in specifying 18C selectivity. We created mSCD1-Y104G to test the hypothesis that eliminating this bulky side chain would create an opening and permit the substrate's methyl end to protrude through the enzyme into the lipid bilayer, facilitating the desaturation of very-long-chain (VLC) substrates. Consistent with this hypothesis, Y104G acquired the ability to desaturate 24C and 26C acyl-CoAs while maintaining its Δ9-regioselectivity. We also investigated two distantly related very-long-chain fatty acyl (VLCFA) desaturases from Arabidopsis, ADS1.2 and ADS1.4, which have Ala and Gly, respectively, in place of the gatekeeping Tyr found in mSCD1. Substitution of Tyr for Ala and Gly in ADS1.2 and ADS1.4, respectively, blocked their ability to desaturate VLCFAs. Further, we identified a pair of fungal desaturase homologs which contained either an Ile or a Gly at this location and showed that only the Gly-containing desaturase was capable of very-long-chain desaturation. The conserved desaturase architecture wherein a surface residue with a single bulky side chain forms the end of the substrate binding cavity predisposes them to single amino acid substitutions that enable a switch between long- and very-long-chain selectivity. The data presented here show that such changes have independently occurred multiple times during evolution.

A Flavone-Based Solvatochromic Probe with A Low Expected Perturbation Impact on the Membrane Physical State.

The study of the cell membrane is an ambitious and arduous objective since its physical state is regulated by a series of processes that guarantee its regular functionality. Among the different methods of analysis, fluorescence spectroscopy is a technique of election, non-invasive, and easy to use. Besides, molecular dynamics analysis (MD) on model membranes provides useful information on the possibility of using a new probe, following its positioning in the membrane, and evaluating the possible perturbation of the double layer. In this work, we report the rational design and the synthesis of a new fluorescent solvatochromic probe and its characterization in model membranes. The probe consists of a fluorescent aromatic nucleus of a 3-hydroxyflavone moiety, provided with a saturated chain of 18 carbon atoms and a zwitterionic head so to facilitate the anchoring to the polar heads of the lipid bilayer and avoid the complete internalization. It was possible to study the behavior of the probe in GUV model membranes by MD analysis and fluorescence microscopy, demonstrating that the new probe can efficiently be incorporated in the lipid bilayer, and give a color response, thanks to is solvatochromic properties. Moreover, MD simulation of the probe in the membrane supports the hypothesis of a reduced perturbation of the membrane physical state.

A 112 Gb/s PAM-4 RX Front-End With Unclocked Decision Feedback Equalizer

The implementation of an unclocked DFE (UC-DFE) architecture for high-speed PAM-4 signals is investigated in this brief. Instead of clocked slicers and flip-flops, data-decision and feedback delay control are performed by saturated analog delay chains. As a result, the UC-DFE, previously exploited for NRZ signals, saves power consumption and silicon area while the simple implementation allows operation at high data-rate. A receiver front-end comprising a linear equalizer and the proposed 2-tap UC-DFE scheme is designed in 7 nm FinFET technology. From post-layout simulations, the receiver recovers a PAM-4 signal at 112 Gb/s after an 18 dB loss channel with a power efficiency of 0.47 pJ/bit. The receiver also works with NRZ signals at half the bit-rate equalizing 24 dB channel loss with a power efficiency of 0.70 pJ/bit.