Membrane Phospholipid Fatty Acid Research Articles

In Staphylococcus aureus, the acyl-CoA synthetase MbcS supports branched-chain fatty acid synthesis from carboxylic acid and aldehyde precursors.

In the human pathogen Staphylococcus aureus, branched-chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids. Strains deficient for BCFAs synthesis experience auxotrophy in laboratory culture and attenuated virulence during infection. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that the overexpression of SAUSA300_2542 (annotated to encode an acyl-CoA synthetase) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched-chain α-keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl-CoA synthetase activity of MbcS activates branched-chain carboxylic acids (BCCAs), and is required by S. aureus to utilize the isoleucine derivative 2-methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched-chain aldehydes into their respective BCCAs and our findings demonstrating that branched-chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous BCCAs and mediates BCFA synthesis via a de novo alternative pathway.

Copper-contaminated soil compromises thermal performance in the springtail Folsomia candida (Collembola)

The widespread agricultural and industrial emissions of copper-based chemicals have increased copper levels in soils worldwide. Copper contamination can cause a range of toxic effects on soil animals and influence thermal tolerance. However, toxic effects are commonly investigated using simple endpoints (e.g., mortality) and acute tests. Thus, how organisms respond to ecological realistic sub-lethal and chronic exposures across the entire thermal scope of an organism is not known. In this study, we investigated the effects of copper exposure on the thermal performance of a springtail (Folsomia candida), regarding its survival, individual growth, population growth, and the composition of membrane phospholipid fatty acids. Folsomia candida (Collembola) is a typical representative of soil arthropods and a model organism that has been widely used for ecotoxicological studies. In a full-factorial soil microcosm experiment, springtails were exposed to three levels of copper (ca. 17 (control), 436, and 1629 mg/kg dry soil) and ten temperatures from 0 to 30 °C. Results showed that three-week copper exposure at temperatures below 15 °C and above 26 °C negatively influenced the springtail survival. The body growth was significantly lower for the springtails in high-dose copper soils at temperatures above 24 °C. A high copper level reduced the number of juveniles by 50 %, thereby impairing population growth. Both temperature and copper exposure significantly impacted membrane properties. Our results indicated that high-dose copper exposure compromised the tolerance to suboptimal temperatures and decreased maximal performance, whereas medium copper exposure partially reduced the performance at suboptimal temperatures. Overall, copper contamination reduced the thermal tolerance of springtails at suboptimal temperatures, probably by interfering with membrane homeoviscous adaptation. Our results show that soil organisms living in copper-contaminated areas might be more sensitive to thermally stressful periods.

Oxidation of Phospholipids by OH Radical Coordinated to Copper Amyloid-β Peptide—A Density Functional Theory Modeling

Oxidative stress and metal dyshomeostasis are considered crucial factors in the pathogenesis of Alzheimer’s disease (AD). Indeed, transition metal ions such as Cu(II) can generate reactive oxygen species (ROS) via O2 Fenton-like reduction, catalyzed by Cu(II) coordinated to the amyloid-beta (Aβ) peptide. Despite intensive efforts, the mechanisms of ROS-induced molecular damage remain poorly understood. In the present paper, we investigate, on the basis of Density Functional Theory (DFT) computations, a possible mechanism of the OH radical propagation toward membrane phospholipid polar head and fatty acid chains starting from the end-product of the OH radical generation by Cu(II)-Aβ. Using phosphatidylcholine as a model of a single unit inside a membrane, we evaluated the thermochemistry of the OH propagation with the oxidation of a C-H bond and the formation of the radical moiety. The DFT results show that Cu(II)-Aβ-OH can oxidize only sn-2 C-H bonds of the polar head and can easily oxidize the C-H bond adjacent to the carbon–carbon double bond in a mono or bis unsaturated fatty acid chain. These results are discussed on the basis of the recent literature on in vitro Aβ metal-catalyzed oxidation and on the possible implications in the AD oxidative stress mechanism.

Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death.

Lipid droplets are fat storage organelles ubiquitously distributed across the eukaryotic kingdom. They have a central role in regulating lipid metabolism and undergo a dynamic turnover of biogenesis and breakdown to meet cellular requirements for fatty acids, including polyunsaturated fatty acids. Polyunsaturated fatty acids esterified in membrane phospholipids define membrane fluidity and can be released by the activity of phospholipases A2 to act as ligands for nuclear receptors or to be metabolized into a wide spectrum of lipid signaling mediators. Polyunsaturated fatty acids in membrane phospholipids are also highly susceptible to lipid peroxidation, which if left uncontrolled leads to ferroptotic cell death. On the one hand, lipid droplets act as antioxidant organelles that control polyunsaturated fatty acid storage in triglycerides in order to reduce membrane lipid peroxidation, preserve organelle function and prevent cell death, including ferroptosis. On the other hand, lipid droplet breakdown fine-tunes the delivery of polyunsaturated fatty acids into metabolic and signaling pathways, but unrestricted lipid droplet breakdown may also lead to the release of lethal levels of polyunsaturated fatty acids. Precise regulation of lipid droplet turnover is thus essential for polyunsaturated fatty acid distribution and cellular homeostasis. In this review, we focus on emerging aspects of lipid droplet-mediated regulation of polyunsaturated fatty acid trafficking, including the management of membrane lipid peroxidation, ferroptosis and lipid mediator signaling.

Biogeochemical properties of blue carbon sediments influence the distribution and monomer composition of bacterial polyhydroxyalkanoates (PHA)

Coastal wetlands are highly efficient ‘blue carbon’ sinks which contribute to mitigating climate change through the long-term removal of atmospheric CO2 and capture of carbon (C). Microorganisms are integral to C sequestration in blue carbon sediments and face a myriad of natural and anthropogenic pressures yet their adaptive responses are poorly understood. One such response in bacteria is the alteration of biomass lipids, specifically through the accumulation of polyhydroxyalkanoates (PHAs) and alteration of membrane phospholipid fatty acids (PLFA). PHAs are highly reduced bacterial storage polymers that increase bacterial fitness in changing environments. In this study, we investigated the distribution of microbial PHA, PLFA profiles, community structure and response to changes in sediment geochemistry along an elevation gradient from intertidal to vegetated supratidal sediments. We found highest PHA accumulation, monomer diversity and expression of lipid stress indices in elevated and vegetated sediments where C, nitrogen (N), PAH and heavy metals increased, and pH was significantly lower. This was accompanied by a reduction in bacterial diversity and a shift to higher abundances of microbial community members favouring complex C degradation. Results presented here describe a connection between bacterial PHA accumulation, membrane lipid adaptation, microbial community composition and polluted C rich sediments.Graphical Geochemical, microbiological and polyhydroxyalkanoate (PHA) gradient in a blue carbon zone.

Allosteric regulation by membranes and hydrophobic subsites in phospholipase A2 enzymes determine their substrate specificity

Lipids play critical roles in several major chronic diseases of our times, including those that involve inflammatory sequelae such as metabolic syndrome including obesity, insulin sensitivity, and cardiovascular diseases. However, defining the substrate specificity of enzymes of lipid metabolism is a challenging task. For example, phospholipase A2 (PLA2) enzymes constitute a superfamily of degradative, biosynthetic, and signaling enzymes that all act stereospecifically to hydrolyze and release the fatty acids of membrane phospholipids. This review focuses on how membranes interact allosterically with enzymes to regulate cell signaling and metabolic pathways leading to inflammation and other diseases. Our group has developed “substrate lipidomics” to quantify the substrate phospholipid specificity of each PLA2 and coupled this with molecular dynamics simulations to reveal that enzyme specificity is linked to specific hydrophobic binding subsites for membrane phospholipid substrates. We have also defined unexpected headgroup and acyl chain specificity for each of the major human PLA2 enzymes, which explains the observed specificity at a structural level. Finally, we discovered that a unique hydrophobic binding site—and not each enzyme’s catalytic residues or polar headgroup binding site—predominantly determines enzyme specificity. We also discuss how PLA2s release specific fatty acids after allosteric enzyme association with membranes and extraction of the phospholipid substrate, which can be blocked by stereospecific inhibitors. After decades of work, we can now correlate PLA2 specificity and inhibition potency with molecular structure and physiological function.

Adipose tissue macrophages and atherogenesis – a synergy with cholesterolaemia

Excessive LDL cholesterol concentration together with subclinical inflammation, in which macrophages play a central role, are linked pathologies. The process starts with the accumulation of macrophages in white adipose tissue and the switch of their polarization toward a pro-inflammatory phenotype. The proportion of pro-inflammatory macrophages in adipose tissue is related to the main risk predictors of cardiovascular disease. The cholesterol content of phospholipids of cell membranes seems to possess a crucial role in the regulation of membrane signal transduction and macrophage polarization. Also, different fatty acids of membrane phospholipids influence phenotypes of adipose tissue macrophages with saturated fatty acids stimulating pro-inflammatory whereas ω3 fatty acids anti-inflammatory changes. The inflammatory status of white adipose tissue, therefore, reflects not only adipose tissue volume but also adipose tissue macrophages feature. The beneficial dietary change leading to an atherogenic lipoprotein decrease may therefore synergically reduce adipose tissue driven inflammation.

Role of fatty acids in inflammation, atherosclerosis, metabolic disorders and gout

Fatty acids (FA) are present in all types of organisms and play an important role in energy metabolism. The length and number of double bonds in the FA of membrane phospholipids determine the viscosity, the activity of transport systems and enzymes, and also the susceptibility to lipid peroxidation. The review discusses the influence of free unsaturated FAs with short and long chains on various inflammatory mechanisms, including atherosclerosis. It has been shown that FAs can reduce endothelial activation and affect the metabolism of eicosanoids. A new model of fundamental factors determining the variability of the timing, degree and duration of acute inflammatory reactions in the deposition of urate crystals in tissues, in which FAs play an important role is considered, using gout as an example. In the future, the study of FAs will expand the understanding of the pathophysiology of chronic inflammation in various diseases, metabolic disorders and atherosclerosis and enable the development of new treatment strategies.

Homeophasic Adaptation in Response to UVA Radiation in Pseudomonas aeruginosa: Changes of Membrane Fatty Acid Composition and Induction of desA and desB Expression.

In bacteria, exposure to changes in environmental conditions can alter membrane fluidity, thereby affecting its essential functions in cell physiology. To adapt to these changes, bacteria maintain appropriate fluidity by varying the composition of the fatty acids of membrane phospholipids, a phenomenon known as homeophasic adaptation. In Pseudomonas aeruginosa, this response is achieved mainly by two mechanisms of fatty acid desaturation: the FabA-FabB and DesA-DesB systems. This study analyzed the effect of ultraviolet-A (UVA) radiation-the major fraction of solar UV radiation reaching the Earth's surface-on the homeophasic process. The prototypical strain PAO1 was grown under sublethal UVA doses or in the dark, and the profiles of membrane fatty acids were compared at early logarithmic, logarithmic and stationary growth phases. In the logarithmic growth phase, it was observed that growth under sublethal UVA doses induced the expression of the desaturase-encoding genes desA and desB and increased the proportion of unsaturated fatty acids; in addition, membrane fluidity could also increase, as suggested by the indices used as indicators of this parameter. The opposite effect was observed in the stationary growth phase. These results demonstrate the relevant role of UVA on the homeophasic response at transcriptional level.

Peony seed oil ameliorates neuroinflammation-mediated cognitive deficits by suppressing microglial activation through inhibition of NF-κB pathway in presenilin 1/2 conditional double knockout mice.

Chronic neuroinflammation has been shown to exert adverse influences on the pathology of Alzheimer's disease (AD), associated with the release of abundant proinflammatory mediators by excessively activated microglia, causing synaptic dysfunction, neuronal degeneration, and memory deficits. Thus, the prevention of microglial activation-associated neuroinflammation is important target for deterring neurodegenerative disorders. Peony seed oil (PSO) is a new food resource, rich in α-linolenic acid, the precursor of long chain omega-3 polyunsaturated fatty acids, including docosahexaenoic acid and eicosapentaenoic acid, which exhibit anti-inflammatory properties by altering cell membrane phospholipid fatty acid compositions, disrupting lipid rafts, and inhibiting the activation of the proinflammatory transcription factor NF-κB. However, few studies have examined the anti-neuroinflammatory effects of PSO in AD, and the relevant molecular mechanisms remain unclear. Presenilin1/2 conditional double knockout (PS cDKO) mice display obvious AD-like phenotypes, such as neuroinflammatory responses, synaptic dysfunction, and cognitive deficits. Here, we assessed the potential neuroprotective effects of PSO against neuroinflammation-mediated cognitive deficits in PS cDKO using behavioral tests and molecular biologic analyses. Our study demonstrated that PSO suppressed microglial activation and neuroinflammation through the down-regulation of proinflammatory mediators, such as inducible NOS, COX-2, IL-1β, and TNF-α, in the prefrontal cortex and hippocampus of PS cDKO mice. Further, PSO significantly lessened memory impairment by reversing hyperphosphorylated tau and synaptic proteins deficits in PS cDKO mice. Importantly, PSO's therapeutic effects on cognitive deficits were due to inhibiting neuroinflammatory responses mediated by NF-κB signaling pathway. Taken together, PSO may represent an effective dietary supplementation to restrain the neurodegenerative processes of AD.

Cytotoxicity of functionalized CeO2 nanoparticles towards Escherichia coli and adaptive response of membrane properties

The cytotoxicity and mechanisms of cerium oxide nanoparticles (CeO2-NPs) on organisms have attracted great concerns recently, while that of CeO2-NPs with functional groups remains unclear. This study investigated cytotoxic effects and mechanisms of CeO2-NPs with hydroxyl, carboxyl, or amino functional groups towards a strain Escherichia coli (E. Coli). Results showed that CeO2-NPs produced a stronger cytotoxicity in NaCl medium than in PBS medium at the concentrations of 10–400 mg/L. The toxicity followed the order of CeO2–COOH > CeO2–NH2 > CeO2–OH. Exposing to CeO2-NPs increased cell membrane permeability and reduced membrane fluidity. The membrane phospholipid fatty acid compositions also varied greatly as a response to the stress of CeO2-NPs, with the proportion of unsaturated fatty acids increased and saturated fatty acids decreased. Both intracellular reactive oxygen species (ROS) level and malonaldehyde (MDA) level declined, suggesting the oxidative stress from ROS may be not the primary reason for the membrane damage. Other mechanisms such as direct membrane oxidation by Ce4+ or physical penetration based on a close contact between nanoparticles and microbes might contribute to the membrane damages and cell viability loss. The present study provides a significant insight into the influence of functionalized CeO2-NPs on a gram-negative bacterium.

Assessment of Plasma Membrane Fatty Acid Composition and Fluidity Using Imaging Flow Cytometry.

Phospholipid fatty acid (FA) composition influences the biophysical properties of the plasma membrane and plays an important role in cellular signaling. Our previous work has demonstrated that plasma membrane fatty acid composition is an important determinant of oncogenic Ras signaling and that dietary (exogenous) modulation of membrane composition may underlie the chemoprotective benefits of long chain n-3 polyunsaturated fatty acids (PUFA). In this chapter, we describe in vitro methods to modulate membrane phospholipid fatty acid composition of cultured cells using fatty acids complexed to bovine serum albumin (BSA). Furthermore, we describe a method to quantify the biophysical properties of plasma membranes in live cells using Di-4-ANEPPDHQ (Di4) and image-based flow cytometry.

<p>Human Secretary Phospholipase A2 Mutations and Their Clinical Implications</p>

Phospholipases A2 (PLA2s) belong to a superfamily of enzymes responsible for hydrolysis of the sn-2 fatty acids of membrane phospholipids to release arachidonic acid. PLA2s are the rate limiting enzyme for the downstream synthesis of prostaglandins and leukotrienes that are the main mediators of inflammation. The extracellular forms of this enzyme are also called the secretary phospholipase A2 (sPLA2) and are distributed extensively in most of the tissues in the human body. Their integral role in inflammatory pathways has been the primary reason for the extensive research on this molecule. The catalytic mechanism of sPLA2 is initiated by a histidine/aspartic acid/calcium complex within the active site. Though they are known to have certain housekeeping functions, certain mutations of sPLA2 are known to be implicated in causation of certain pathologies leading to diseases such as atherosclerosis, cardiovascular diseases, benign fleck retina, neurodegeneration, and asthma. We present an overview of human sPLA2 and a comprehensive compilation of the mutations that result in various disease phenotypes. The study not only helps to have a holistic understanding of human sPLA2 mutations and their clinical implications, but is also a useful platform to initiate research pertaining to structure–function relationship of the mutations to develop effective therapies for management of these diseases.

Mercury (Hg2+) interferes with physiological adaptations to freezing in the arctic earthworm Enchytraeus albidus

Freezing temperatures is an important stressor in the arctic regions and has a significant influence on the population dynamics and geographic distribution of terrestrial invertebrates. Toxic metals in the environment can interfere with protective cold-acclimation responses of organisms. It is therefore important to evaluate the combined effects of cold stress and environmental contaminants. Here, we aimed to investigate the effects of Hg (HgCl2) on various physiological aspects of freeze-tolerance in the earthworm (Enchytraeus albidus). We measured the levels of the cryoprotectant glucose, the glycogen content (source of glucose molecules for cryoprotection and fuel for metabolism), and changes in the composition of membrane phospholipid fatty acids (PLFA) as an indicator of lipid peroxidation.Freezing at −6 °C had no effect on survival in uncontaminated soil, however, survival of freezing in Hg contaminated soil was clearly reduced, especially at extended exposure times. Thus, the LC50 value in frozen soil decreased from 8.3 mg Hg kg−1 (when exposed for 17 days) to only 4.2 mg Hg kg−1 after 36 days’ exposure indicating that combined effects of Hg and freezing became larger at prolonged exposure times. Hg caused a depletion of glycogen reserves (almost 50% at 12 mg kg−1 dry soil), but despite this effect worms were able to maintain a constant cryoprotectant level (about 0.12 mg glucose mg−1 dry weight) at all Hg concentrations. Hg had clear negative effects on the proportion of unsaturated PLFAs, which could be an indication of lipid peroxidation. Since a high proportion of unsaturated fatty acids in the membrane is important for invertebrate freeze-tolerance, our results suggest that the negative effect of Hg on freeze-tolerance in E. albidus is related to degraded membrane functionality at low temperature.

Enhanced azo dye biodegradation performance and halotolerance of Candida tropicalis SYF-1 by static magnetic field (SMF)

Enhancing Acid Red B (ARB) decolorization by growing cells of a halotolerant yeast Candida tropicalis SYF-1 with static magnetic field (SMF) was investigated. Activity of key enzymes and membrane phospholipid fatty acids (PLFAs) were analyzed for estimating the change of metabolic activity and membrane salt-stress response, respectively. Possible enhancement mechanisms were revealed through comparative transcriptome analysis. The results showed that 95.0 mT SMF enhanced ARB decolorization by growing cells of a yeast SYF-1, as well as cell growth and halotolerance capability. Activity of intracellular lignin peroxidase (LiP) and laccase (Lac) was 1.51- and 1.47-fold higher with 95.0 mT SMF than that without SMF, respectively. Unsaturation degree and chain length of dominant PLFAs was increased by 95.0 mT SMF treatment. Several functional protein encoding unigenes related to organics biodegradation, cell growth and halotolerance were 1.17- to 4.19-fold up-regulated in response to 95.0 mT SMF.

Docosahexaenoic acid varies in rat skeletal muscle membranes according to fibre type and provision of dietary fish oil

BackgroundDietary fish oil provides polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and is associated with modified oxygen consumption, contractile fatigue and physiological responses to ischaemia or hypoxia in striated muscle. This study systematically investigated the membrane incorporation of fatty acids, with a focus on DHA, into skeletal muscle in relation to functional/metabolic differences and their responsiveness to fish oil doses. MethodsMale Sprague-Dawley rats were randomised to isoenergetic diets (10% fat by weight). Human Western-style diets were simulated with 5.5% tallow, 2.5% n-6 PUFA sunflower seed oil and 2% olive oil (Control). High-DHA tuna oil exchanged for olive oil provided a Low (0.32%) or moderate (Mod) (1.25%) fish oil diet. Membrane phospholipid fatty acid composition was analysed in samples of five skeletal muscles selected for maximum variation in muscle fibre-type. ResultsConcentrations of DHA varied according to muscle fibre type, very strongly associated with fast oxidative glycolytic fibre population (r2 = 0.93; P < 0.01). No relationship was evident between DHA and fast glycolytic or slow oxidative fibre populations. Fish oil diets increased membrane incorporation of DHA in all muscles, mainly at the expense of n-6 PUFA linoleic and arachidonic acid. ConclusionThe exquisite responsiveness of all skeletal muscles to as little fish oil as the equivalent of 1–2 fish meals per week in a human diet and the selective relationship to fatigable muscle fibre-types supports an integral role for DHA in muscle physiology, and particularly in fatigue resistance of fast-twitch muscles. SummarySkeletal muscle fibres vary according to structural, metabolic and neurological characteristics and ultimately influences contractile function. This study sort to determine if the composition of phospholipid polyunsaturated fatty acids (PUFA), incorporated in their membranes, might also differ according to fibre type and when omega-3 PUFA are made available in the diet. We systematically demonstrated that the omega-3 PUFA, docosahexaenoic acid (DHA), incorporated into skeletal muscle membranes well above its provision in the diet and without competitive influence of high omega-6 PUFA concentrations, typical to the Western-style human diet. Notably, incorporation preferentially occurred according to metabolic characteristics of each muscle, supporting the notion that DHA plays an integral role in fast oxidative glycolytic muscle fibres.

Microbial utilization of simple carbon substrates in boreal peat soils at low temperatures

Boreal peatlands are key high-latitude ecosystem types and act as a carbon (C) sink storing an estimated 25% of the world's soil C. These environments are currently seeing the most substantial changing climate, especially during the winter. CO2 emissions during the winter can correspond to 80% of the growing season's net CO2 assimilation. Yet, our conceptual understanding of the controls on microbial metabolic activity in peat soils at temperatures ≤0 °C is poor. We used stable isotope probing of peat samples and tracked the fate of 13C-glucose using 13C-NMR. We show that microorganisms in frozen boreal peat soils utilize monomeric C-substrates to sustain both catabolic and anabolic metabolism at temperatures down to −5 °C. The 13C-substrate was transformed into 13C–CO2, different metabolites, and incorporated into membrane phospholipid fatty acids. The 16S rRNA-based community analyses revealed the activity at −3 °C changes the composition of the bacterial community over relevant timescales. Below 0 °C, small temperature changes have strong effects on process rates and small differences in winter soil temperature may affect C dynamics of northern peatlands. Understanding biological processes at low and below zero temperatures are central for the overall functioning of these systems representing one of the world's major soil C pools.

The role of phospholipase A2 in multiple Sclerosis: A systematic review and meta-analysis

Phospholipases A2 (PLA2) are a diverse group of enzymes that cleave the fatty acids of membrane phospholipids. They play critical roles in pathogenesis of neurodegenerative diseases such as multiple sclerosis by enhancing oxidative stress and initiating inflammation. The levels of PLA2 activity in MS patients compared to controls and role of inhibiting PLA2 activity on severity scores in different experimental models are not comprehensively assessed in the light of varying evidence from published studies. The objective of this systematic review is to determine the association between PLA2 activity and multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). We performed a systematic review of six studies that assessed PLA2 activity in MS patients compared to controls and nine studies that assessed PLA2 activity in EAE. sPLA2 nor Lp-PLA2 activity were not increased in MS compared to controls in five of those six studies. A difference in sPLA2 activity was only found in a study that measured the enzyme activity in urine. However, inhibiting cPLA2 or sPLA2 led to lower clinical severity or no signs of EAE in mice, and a lower incidence of EAE lesions compared to animals without cPLA2 inhibition. These findings indicate that PLA2 appears to play a role in the pathogenesis of EAE.

Liver X receptors in lipid signalling and membrane homeostasis.

Liver X receptors α and β (LXRα and LXRβ) are nuclear receptors with pivotal roles in the transcriptional control of lipid metabolism. Transcriptional activity of LXRs is induced in response to elevated cellular levels of cholesterol. LXRs bind to and regulate the expression of genes that encode proteins involved in cholesterol absorption, transport, efflux, excretion and conversion to bile acids. The coordinated, tissue-specific actions of the LXR pathway maintain systemic cholesterol homeostasis and regulate immune and inflammatory responses. LXRs also regulate fatty acid metabolism by controlling the lipogenic transcription factor sterol regulatory element-binding protein 1c and regulate genes that encode proteins involved in fatty acid elongation and desaturation. LXRs exert important effects on the metabolism of phospholipids, which, along with cholesterol, are major constituents of cellular membranes. LXR activation preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids by inducing transcription of the remodelling enzyme lysophosphatidylcholine acyltransferase 3. The ability of the LXR pathway to couple cellular sterol levels with the saturation of fatty acids in membrane phospholipids has implications for several physiological processes, including lipoprotein production, dietary lipid absorption and intestinal stem cell proliferation. Understanding how LXRs regulate membrane composition and function might provide new therapeutic insight into diseases associated with dysregulated lipid metabolism, including atherosclerosis, diabetes mellitus and cancer.

Coping with arsenic stress: Adaptations of arsenite-oxidizing bacterial membrane lipids to increasing arsenic levels.

Elevated levels of arsenic (As) in aquifers of South East Asia have caused diverse health problems affecting millions of people who drink As‐rich groundwater and consume various contaminated agriculture products. The biogeochemical cycling and mobilization/immobilization of As from its mineral‐bound phase is controlled by pH, oxic/anoxic conditions, and different microbial processes. The increased As flux generated from ongoing biogeochemical processes in the subsurface in turn affects the in situ microbial communities. This study analyzes how the indigenous arsenite‐oxidizing bacteria combat As stress by various biophysical alterations and self‐adaptation mechanisms. Fifteen arsenite‐oxidizing bacterial strains were isolated and identified using a polyphasic approach. The bacterial strains isolated from these aquifers belong predominantly to arsenite‐oxidizing bacterial groups. Of these, the membrane‐bound phospholipid fatty acids (PLFA) were characterized in seven selected bacterial isolates grown at different concentrations of As(III) in the medium. One of the significant findings of this study is how the increase in external stress can induce alteration of membrane PLFAs. The change in fatty acid saturation and alteration of their steric conformation suggests alteration of membrane fluidity due to change in As‐related stress. However, different bacterial groups can have different degrees of alteration that can affect sustainability in As‐rich aquifers of the Bengal Delta Plain.