scholarly journals A Phantom System Designed to Assess the Effects of Membrane Lipids on Water Proton Relaxation

2018 ◽  
Author(s):  
Oshrat Shtangel ◽  
Aviv A. Mezer
Keyword(s):  
Membrane Lipids ◽  
Magnetization Transfer ◽  
Membrane Lipid ◽  
Water Proton ◽  
Proton Relaxation ◽  
Proton Density ◽  
Brain Lipids ◽  
Water Fraction ◽  
Lipid Environment

AbstractPurposeQuantitative magnetic resonance imaging (qMRI) provides a method for the non-invasive study of brain structure and associated changes, expressed in physical units. qMRI parameters have been shown to reflect brain tissue composition such as myelin. Nevertheless, it remains a major challenge to identify and quantify the contributions of specific molecular components to the MRI signal. Here, we describe a phantom system that can be used to evaluate the contribution of human brain lipids to qMRI parameters.MethodsA thin layer evaporation-hydration technique was used to formulate liposomes that mimic the physiological bi-layered membrane lipid environment. We then applied quantitative clinical MRI techniques with adjusted bias corrections in order to test the ability of the phantom system to estimate multiple qMRI parameters such as proton density (PD), T1, T2, T2* and magnetization transfer (MT).ResultsThe results indicated that phantoms composed of various lipids could provide a stable and reliable estimation of qMRI parameters. In addition, the calculated water fraction (WF) maps for the phantoms were found to accurately represent the true WF volumes.ConclusionWe have successfully created a biologically relevant liposome phantom system whose lipid composition can be fully controlled. This system can be used to measure the contributions of lipids to qMRI parameters under conditions that are relevant to in-vivo human scans.

scholarly journals Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

2021 ◽  
Vol 7 (7) ◽  
pp. 514
Author(s):  
Mariangela Dionysopoulou ◽  
George Diallinas
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Aspergillus Nidulans ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lipid Biosynthesis ◽  
Transport Kinetics ◽  
Negative Effect ◽  
And Function

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.

scholarly journals Survey of water proton longitudinal relaxation in liver in vivo

2021 ◽  
Author(s):  
John Charles Waterton
Keyword(s):  
Normal Liver ◽  
Population Variation ◽  
Water Proton ◽  
Proton Relaxation ◽  
Literature Searching ◽  
Repeatability Error ◽  
Coefficients Of Variation ◽  
Weighted Means ◽  
Propagation Of Errors

Abstract Objective To determine the variability, and preferred values, for normal liver longitudinal water proton relaxation rate R1 in the published literature. Methods Values of mean R1 and between-subject variance were obtained from literature searching. Weighted means were fitted to a heuristic and to a model. Results After exclusions, 116 publications (143 studies) remained, representing apparently normal liver in 3392 humans, 99 mice and 249 rats. Seventeen field strengths were included between 0.04 T and 9.4 T. Older studies tended to report higher between-subject coefficients of variation (CoV), but for studies published since 1992, the median between-subject CoV was 7.4%, and in half of those studies, measured R1 deviated from model by 8.0% or less. Discussion The within-study between-subject CoV incorporates repeatability error and true between-subject variation. Between-study variation also incorporates between-population variation, together with bias from interactions between methodology and physiology. While quantitative relaxometry ultimately requires validation with phantoms and analysis of propagation of errors, this survey allows investigators to compare their own R1 and variability values with the range of existing literature.

scholarly journals Dynamic modulation of mitochondrial membrane physical properties and ATPase activity by diet lipid

1981 ◽  
Vol 198 (1) ◽  
pp. 167-175 ◽  
Author(s):  
S M Innis ◽  
M T Clandinin
Keyword(s):  
Fatty Acid ◽  
Rapeseed Oil ◽  
Membrane Lipid ◽  
Dietary Lipid ◽  
Soya Bean ◽  
The Body ◽  
Kinetic Properties ◽  
Mitochondrial Atpase ◽  
Lipid Environment

A longitudinal cross-over feeding design was used to investigate the relationship of dietary lipid composition to the membrane lipid environment and activity of mitochondrial ATPase in vivo. Rats were fed a polyunsaturated fatty-acid-rich oil (soya-bean oil) for 12 days, crossed-over to a monounsaturated fatty-acid-rich oil (rapeseed oil) for the next 11 days, then returned to soya-bean oil for 11 more days. Additional rats were fed either soya-bean oil or rapeseed oil throughout. Rats fed rapeseed oil had lower rates of ATPase-catalysed ATP/[32P]Pi exchange than rats fed soya-bean oil. Arrhenius plots showed higher transition temperature (Tt) and activation energy (Ea) for rats fed rapeseed oil. Switching from soya-bean oil to rapeseed oil was dynamically followed by changes in the thermotropic and kinetic properties of the mitochondrial ATPase exchange reaction. Returning to soya-bean oil reversed these changes. The rapid and reversible modulation of Tt caused by a change of the type of fat ingested suggests that membrane physicochemical properties are not under rigid intrinsic control but are continually modified by the profile of exogenously derived fatty acids. The studies suggest that in vivo the activity of mitochondrial ATPase is in part determined by dietary lipid via its influence on the microenvironment of the enzyme. The rapidity and ready reversibility of changes observed for this subcellular-membrane-bound enzyme suggest that dietary fatty-acid balance may be an important determinant of other membrane functions in the body.

Pathological basis of diffusely abnormal white matter: insights from magnetic resonance imaging and histology

2010 ◽  
Vol 17 (2) ◽  
pp. 144-150 ◽  
Author(s):  
Cornelia Laule ◽  
Irene M Vavasour ◽  
Esther Leung ◽  
David KB Li ◽  
Piotr Kozlowski ◽  
...  
Keyword(s):  
White Matter ◽  
Magnetization Transfer ◽  
Selective Reduction ◽  
Myelin Proteins ◽  
Water Fraction ◽  
Normal Appearing White Matter ◽  
Three Samples ◽  
Disability Status ◽  
Myelin Water Fraction

Background: The pathological basis of diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) has not been elucidated in detail, but may be an important element in disability and clinical progression. Methods: Fifty-three subjects with MS were examined with T1, multi-echo T2 and magnetization transfer (MT). Twenty-three samples of formalin-fixed MS brain tissue were examined with multi-echo T2 and subsequently stained for myelin phospholipids using luxol fast blue, for axons using Bielschowsky, immunohistochemically for the myelin proteins myelin basic protein (MBP) and 2′,3′-cyclic nucleotide 3′ phosphohydrolase (CNP) and for astrocytes using glial fibrillary acidic protein (GFAP). Regions of interest in DAWM were compared with normal appearing white matter. Results: Fourteen of 53 subjects with MS in the in vivo study showed the presence of DAWM. Subjects with DAWM were found to have a significantly lower Expanded Disability Status Scale (EDSS) and shorter disease duration (DD) when compared with subjects without DAWM (EDSS: 1.5 versus 3.0, p = 0.031; DD: 5.4 versus 10.3 years, p = 0.045). DAWM in vivo had reduced myelin water and MT ratio, and increased T2 and water content. Histological analysis suggests DAWM, which shows a reduction of the myelin water fraction, is characterized by selective reduction of myelin phospholipids, but with a relative preservation of myelin proteins and axons. Conclusions: These findings suggest that the primary abnormality in DAWM is a reduction or perturbation of myelin phospholipids that correlates with a reduction of the myelin water fraction.

scholarly journals Modulation Effects of Curcumin on Erythrocyte Ion-Transporter Activity

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Prabhakar Singh ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Membrane Lipids ◽  
Curcuma Longa ◽  
Membrane Lipid ◽  
Membrane Transporters ◽  
Protective Mechanism ◽  
Lipid Hydroperoxides ◽  
Beneficial Effects

Curcumin ((1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), the yellow biphenolic pigment isolated from turmeric (Curcuma longa), has various medicinal benefits through antioxidation, anti-inflammation, cardiovascular protection, immunomodulation, enhancing of the apoptotic process, and antiangiogenic property. We explored the effects of curcuminin vitro(10−5 M to 10−8 M) andin vivo(340 and 170 mg/kg b.w., oral) on Na+/K+ATPase (NKA), Na+/H+exchanger (NHE) activity, and membrane lipid hydroperoxides (ROOH) in control and experimental oxidative stress erythrocytes of Wistar rats. As a result, we found that curcumin potently modulated the membrane transporters activity with protecting membrane lipids against hydro-peroxidation in control as well as oxidatively challenged erythrocytes evidenced by stimulation of NKA, downregulation of NHE, and reduction of ROOH in the membrane. The observed results corroborate membrane transporters activity with susceptibility of erythrocyte membrane towards oxidative damage. Results explain the protective mechanism of curcumin against oxidative stress mediated impairment in ions-transporters activity and health beneficial effects.

scholarly journals Membrane Interactivity of Non-steroidal Anti-inflammatory Drugs: A Literature Review

2020 ◽  
pp. 1-30
Author(s):  
Hironori Tsuchiya ◽  
Maki Mizogami
Keyword(s):  
Membrane Fluidity ◽  
Membrane Lipids ◽  
Direct Interaction ◽  
Membrane Lipid ◽  
Lipid Phase ◽  
Lipid Bilayer Membranes ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Background: Although the mode of action of non-steroidal anti-inflammatory drugs (NSAIDs) has been exclusively referred to as inhibition of cyclooxygenase, their broad pharmacological and toxicological spectra are not necessarily interpreted by the direct interaction with such enzyme proteins. Aims: Since NSAIDs have the common amphiphilic structure, they have the possibility of acting on membrane-constituting lipids. In order to gain insights into the additional mechanism of NSAIDs, we reviewed their membrane interactivity to modify the physicochemical properties of membranes. Methodology: We retrieved scientific articles from PubMed/MEDLINE, Google Scholar and ACS Publications by searching databases from 1990 to 2019. Research papers published in English in the internationally recognized journals and on-line journals were cited with preference to more recent publications. Collected articles were reviewed by title, abstract and text for relevance. Results: Results of the literature search indicated that NSAIDs structure-specifically cause the in vitro and in vivo interactions with artificial and biological membranes to change membrane fluidity, lipid phase transition and permeability. The features and potencies of their membrane interactivity vary depending on drug concentration, medium pH and membrane lipid composition. In addition to membrane proteins, NSAIDs act on membrane lipids to exhibit the anti-inflammatory and anti-tumor activity by interacting with lipid bilayer membranes at relatively low concentrations to decrease membrane fluidity and thereby affect the enzymatic activity of membrane-associated proteins and to exhibit the gastrointestinal and cardiovascular toxicity by interacting with membranous phospholipids at relatively high concentrations to increase membrane fluidity and thereby impair the membrane-relevant biofunctions. Other diverse effects of NSAIDs may also be related to their membrane interactions. Conclusion: NSAIDs share the membrane interactivity common to them as one of possible pharmacological and toxicological mechanisms.            

scholarly journals A technique for 3D in vivo quantification of proton density and magnetization transfer coefficients of knee joint cartilage

2000 ◽  
Vol 8 (6) ◽  
pp. 426-433 ◽  
Author(s):  
J Hohe ◽  
S Faber ◽  
T Stammberger ◽  
M Reiser ◽  
K.-H Englmeier ◽  
...  
Keyword(s):  
Knee Joint ◽  
Magnetization Transfer ◽  
Proton Density ◽  
Joint Cartilage ◽  
Transfer Coefficients

scholarly journals Drug Susceptibilities of Yeast Cells Are Affected by Membrane Lipid Composition

2002 ◽  
Vol 46 (12) ◽  
pp. 3695-3705 ◽  
Author(s):  
Kasturi Mukhopadhyay ◽  
Avmeet Kohli ◽  
Rajendra Prasad
Keyword(s):  
Membrane Fluidity ◽  
Membrane Lipids ◽  
Drug Susceptibility ◽  
Membrane Lipid ◽  
Yeast Cells ◽  
Wild Type ◽  
Enhanced Diffusion ◽  
The Status ◽  
Lipid Environment ◽  
Nitroquinoline Oxide

ABSTRACT In the present study we have exploited isogenic erg mutants of Saccharomyces cerevisiae to examine the contribution of an altered lipid environment on drug susceptibilities of yeast cells. It is observed that erg mutants, which possess high levels of membrane fluidity, were hypersensitive to the drugs tested, i.e., cycloheximide (CYH), o-phenanthroline, sulfomethuron methyl, 4-nitroquinoline oxide, and methotrexate. Most of the erg mutants except mutant erg4 were, however, resistant to fluconazole (FLC). By using the fluorophore rhodamine-6G and radiolabeled FLC to monitor the passive diffusion, it was observed that erg mutant cells elicited enhanced diffusion. The addition of a membrane fluidizer, benzyl alcohol (BA), to S. cerevisiae wild-type cells led to enhanced membrane fluidity. However, a 10 to 12% increase in BA-induced membrane fluidity did not alter the drug susceptibilities of the S. cerevisiae wild-type cells. The enhanced diffusion observed in erg mutants did not seem to be solely responsible for the observed hypersensitivity of erg mutants. In order to ascertain the functioning of drug extrusion pumps encoding the genes CDR1 (ATP-binding cassette family) and CaMDR1 (MFS family) of Candida albicans in a different lipid environment, they were independently expressed in an S. cerevisiae erg mutant background. While the fold change in drug resistance mediated by CaMDR1 remained the same or increased in erg mutants, susceptibility to FLC and CYH mediated by CDR1 was increased (decrease in fold resistance). Our results demonstrate that between the two drug extrusion pumps, Cdr1p appeared to be more adversely affected by the fluctuations in the membrane lipid environment (particularly to ergosterol). By using 6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino-hexanoyl] sphingosyl phosphocholine (a fluorescent analogue of sphingomyelin), a close interaction between membrane ergosterol and sphingomyelin which appears to be disrupted in erg mutants is demonstrated. Taken together it appears that multidrug resistance in yeast is closely linked to the status of membrane lipids, wherein the overall drug susceptibility phenotype of a cell appears to be an interplay among drug diffusion, extrusion pumps, and the membrane lipid environment.

scholarly journals New insights into the dynamic development of the cerebral cortex in childhood and adolescence: Integrating macro- and microstructural MRI findings

2020 ◽  
Author(s):  
Linn B. Norbom ◽  
Lia Ferschmann ◽  
Nadine Parker ◽  
Ingrid Agartz ◽  
Ole A. Andreassen ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cognitive Abilities ◽  
Common Mental Disorders ◽  
Ex Vivo ◽  
Magnetization Transfer ◽  
Microstructural Development ◽  
Childhood And Adolescence ◽  
Mri Findings ◽  
Water Fraction

Through dynamic transactional processes between genetic and environmental factors, childhood and adolescence involve reorganization and optimization of the cerebral cortex. The cortex and its development plays a crucial role for prototypical human cognitive abilities. At the same time, many common mental disorders appear during these critical phases of neurodevelopment. Magnetic resonance imaging (MRI) can indirectly capture several multifaceted changes of cortical macro- and microstructure, of high relevance to further our understanding of the neural foundation of cognition and mental health. Great progress has been made recently in mapping the typical development of cortical morphology. Moreover, newer less explored MRI signal intensity and specialized quantitative T2 measures have been applied to assess microstructural cortical development. We review recent findings of typical postnatal macro- and microstructural development of the cerebral cortex from early childhood to young adulthood. We cover studies of cortical volume, thickness, area, gyrification, T1-weighted (T1w) tissue contrasts such a grey/white matter contrast, T1w/T2w ratio, magnetization transfer and myelin water fraction. Finally, we integrate imaging studies with cortical gene expression findings to further our understanding of the underlying neurobiology of the developmental changes, bridging the gap between ex vivo histological- and in vivo MRI studies.

scholarly journals In Vivo Assay Reveals Microbial OleA Thiolases Initiating Hydrocarbon and β-Lactone Biosynthesis

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Megan D. Smith ◽  
Serina L. Robinson ◽  
Mandkhai Molomjamts ◽  
Lawrence P. Wackett
Keyword(s):  
Metabolic Pathways ◽  
Xanthomonas Campestris ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Limited Information ◽  
Content Type ◽  
Bacterial Phyla ◽  
Long Chain

ABSTRACT OleA, a member of the thiolase superfamily, is known to catalyze the Claisen condensation of long-chain acyl coenzyme A (acyl-CoA) substrates, initiating metabolic pathways in bacteria for the production of membrane lipids and β-lactone natural products. OleA homologs are found in diverse bacterial phyla, but to date, only one homodimeric OleA has been successfully purified to homogeneity and characterized in vitro. A major impediment for the identification of new OleA enzymes has been protein instability and time-consuming in vitro assays. Here, we developed a bioinformatic pipeline to identify OleA homologs and a new rapid assay to screen OleA enzyme activity in vivo and map their taxonomic diversity. The screen is based on the discovery that OleA displayed surprisingly high rates of p-nitrophenyl ester hydrolysis, an activity not shared by other thiolases, including FabH. The high rates allowed activity to be determined in vitro and with heterologously expressed OleA in vivo via the release of the yellow p-nitrophenol product. Seventy-four putative oleA genes identified in the genomes of diverse bacteria were heterologously expressed in Escherichia coli, and 25 showed activity with p-nitrophenyl esters. The OleA proteins tested were encoded in variable genomic contexts from seven different phyla and are predicted to function in distinct membrane lipid and β-lactone natural product metabolic pathways. This study highlights the diversity of unstudied OleA proteins and presents a rapid method for their identification and characterization. IMPORTANCE Microbially produced β-lactones are found in antibiotic, antitumor, and antiobesity drugs. Long-chain olefinic membrane hydrocarbons have potential utility as fuels and specialty chemicals. The metabolic pathway to both end products share bacterial enzymes denoted as OleA, OleC, and OleD that transform acyl-CoA cellular intermediates into β-lactones. Bacteria producing membrane hydrocarbons via the Ole pathway additionally express a β-lactone decarboxylase, OleB. Both β-lactone and olefin biosynthesis pathways are initiated by OleA enzymes that define the overall structure of the final product. There is currently very limited information on OleA enzymes apart from the single representative from Xanthomonas campestris. In this study, bioinformatic analysis identified hundreds of new, putative OleA proteins, 74 proteins were screened via a rapid whole-cell method, leading to the identification of 25 stably expressed OleA proteins representing seven bacteria phyla.

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