135 research outputs found
DHA Alters Raft-like Membrane Domains as Revealed by Solid State 2H NMR Spectroscopy
poster abstractDietary omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic acid (DHA, 22:6), are correlated with the prevention of neurological and autoimmune disorders in humans. These fatty acids must be obtained from the diet, such as oil fish or fish oil supplements, as they cannot be generated within the human body. The origin of the health benefits at the molecular level is still under question. A membrane-mediated mechanism in which n-3 PUFAs are incorporated into phospholipids and modulate molecular organization is one possibility. Cellular membranes are inhomogeneous where structurally diverse lipids can exist in separate domains. Regions rich in sphingomyelin (SM) and cholesterol, commonly called lipid rafts, contain important signaling proteins. In a recent solid-state 2H nuclear magnetic resonance (2H NMR) study of a model membrane composed of 1-[2H31] palmitoyl-2-docosahexaenoyl-phosphatidylcholine (PDPC-d31), a deuterated analog of a DHA-containing phospholipid, in mixtures with SM and cholesterol, we discovered that DHA could significantly enter raft-like domains. How DHA affects the molecular organization within the raft-like domains is addressed here by observing PSM-d31, an analog of SM with a perdeuterated N-palmitoyl chain. The 2H NMR spectra for PSM-d31, in mixtures with PDPC and cholesterol, exhibit two spectral components, a larger more ordered component that we attribute to raft-like domains and a smaller less ordered component that we attribute to non-raft-like domains. On average, the order of PSM-d31 is reduced and, thus, disordering of PSM-d31 by PDPC is indicated. Our observations confirm that DHA can infiltrate rafts and affect molecular organization, which has implications for the signaling of raft and non-raft proteins. Furthermore, these results are consistent with in vivo studies showing that DHA infiltrates rafts
Raft Busters: A Molecular Role for DHA in Biological Membranes?
poster abstractDietary consumption of fish oils rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic acid (DHA, 22:6), has a wide variety of health benefits. However, a complete molecular mechanism is yet to be elucidated. One model that has emerged from biochemical and imaging studies of cells postulates that n-3 PUFAs are taken up into phospholipids in the plasma membrane of cells and, due to their high disorder and aversion for cholesterol, reorganize lipid rafts. Lipid rafts are ordered domains within biological membranes which contain high amounts of sphingomyelin (SM) and cholesterol. To investigate this model, we studied lipid bilayers composed of SM, PDPC (a DHA-containing phospholipid), and cholesterol (1:1:1 mol). The molecular organization of each lipid was investigated with solid-state 2H NMR using deuterated analogs of the lipids. Spectral components assigned to ordered raft-like domains and disordered non-raft domains were resolved, from which the composition of the domains and the order within them could be determined. Most of the SM (84%) and cholesterol (88%) was found in the raft-like domain, together with a substantial amount of PDPC (70%). Despite the infiltration of PDPC there appears to be minimal effect on the order of SM or cholesterol. We speculate that PDPC molecules sequester into small groups minimizing the contact of DHA chains with cholesterol, thereby interrupting the continuity of the raft-like environment
DHA and EPA Interaction with Raft Domains Observed With Solid-State 2H NMR Spectroscopy
poster abstractResearch continues to examine the health benefits of omega-3 polyunsaturated fatty acids (n-3 PUFA) found in fish oils. The major bioactive components are eicosapentaenoic acid (EPA, 20:5), with 20 carbons and 5 double bonds, and docosahexaenoic acid (DHA, 22:6), with 22 carbons and 6 double bonds. However, their molecular modes of action remain unclear. A suggested hypothesis is that these fatty acids are incorporated into membrane phospholipids and modify the structure and organization of lipid rafts, thus affecting cell signaling. We used solid-state 2H NMR spectroscopy to compare molecular organization in mixtures of 1-palmitoyl-2-eicosapentaenoylphosphatidylcholine (PEPC) and 1-palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC) with the raft-stabilizing molecules sphingomyelin (SM) and cholesterol. Our spectra for PEPC-d31 and PDPC-d31, analogs of PEPC and PDPC with a perdeuterated palmitoyl sn-1 chain, showed that DHA has a greater tendency than EPA to incorporate into raft-like domains enriched in SM and cholesterol. By using PSM-d31, an analog of SM with a perdeuterated N-palmitoyl chain, we now directly observe one of the raft-forming molecules and analyze the molecular order within the raft. These results will add to the growing information on how EPA and DHA differentially modify lipid domain organization in bilayers
2D Signal Estimation for Sparse Distributed Target Photon Counting Data
In this study, we explore the utilization of maximum likelihood estimation
for the analysis of sparse photon counting data obtained from distributed
target lidar systems. Specifically, we adapt the Poisson Total Variation
processing technique to cater to this application. By assuming a Poisson noise
model for the photon count observations, our approach yields denoised estimates
of backscatter photon flux and related parameters. This facilitates the
processing of raw photon counting signals with exceptionally high temporal and
range resolutions (demonstrated here to 50 Hz and 75 cm resolutions), including
data acquired through time-correlated single photon counting, without
significant sacrifice of resolution. Through examination involving both
simulated and real-world 2D atmospheric data, our method consistently
demonstrates superior accuracy in signal recovery compared to the conventional
histogram-based approach commonly employed in distributed target lidar
applications
Classical simulation of measurement-based quantum computation on higher-genus surface-code states
We consider the efficiency of classically simulating measurement-based
quantum computation on surface-code states. We devise a method for calculating
the elements of the probability distribution for the classical output of the
quantum computation. The operational cost of this method is polynomial in the
size of the surface-code state, but in the worst case scales as in the
genus of the surface embedding the code. However, there are states in the
code space for which the simulation becomes efficient. In general, the
simulation cost is exponential in the entanglement contained in a certain
effective state, capturing the encoded state, the encoding and the local
post-measurement states. The same efficiencies hold, with additional
assumptions on the temporal order of measurements and on the tessellations of
the code surfaces, for the harder task of sampling from the distribution of the
computational output.Comment: 21 pages, 13 figure
Differential Requirement for Utrophin in the Induced Pluripotent Stem Cell Correction of Muscle versus Fat in Muscular Dystrophy Mice
Duchenne muscular dystrophy (DMD) is an incurable degenerative muscle disorder. We injected WT mouse induced pluripotent stem cells (iPSCs) into mdx and mdxβΆutrophin mutant blastocysts, which are predisposed to develop DMD with an increasing degree of severity (mdx <<< mdxβΆutrophin). In mdx chimeras, iPSC-dystrophin was supplied to the muscle sarcolemma to effect corrections at morphological and functional levels. Dystrobrevin was observed in dystrophin-positive and, at a lesser extent, utrophin-positive areas. In the mdxβΆutrophin mutant chimeras, although iPSC-dystrophin was also supplied to the muscle sarcolemma, mice still displayed poor skeletal muscle histopathology, and negligible levels of dystrobrevin in dystrophin- and utrophin-negative areas. Not only dystrophin-expressing tissues are affected by iPSCs. Mdx and mdxβΆutrophin mice have reduced fat/body weight ratio, but iPSC injection normalized this parameter in both mdx and mdxβΆutrophin chimeras, despite the fact that utrophin was compromised in the mdxβΆutrophin chimeric fat. The results suggest that the presence of utrophin is required for the iPSC-corrections in skeletal muscle. Furthermore, the results highlight a potential (utrophin-independent) non-cell autonomous role for iPSC-dystrophin in the corrections of non-muscle tissue like fat, which is intimately related to the muscle
Last Men Standing: Chlamydatus Portraits and Public Life in Late Antique Corinth
Notable among the marble sculptures excavated at Corinth are seven portraits of men wearing the long chlamys of Late Antique imperial office. This unusual costume, contemporary portrait heads, and inscribed statue bases all help confirm that new public statuary was created and erected at Corinth during the 4th and 5th centuries. These chlamydatus portraits, published together here for the first time, are likely to represent the Governor of Achaia in his capital city, in the company of local benefactors. Among the last works of the ancient sculptural tradition, they form a valuable source of information on public life in Late Antique Corinth
Incorporation of a Dietary Omega 3 Fatty Acid Impairs Murine Macrophage Responses to Mycobacterium tuberculosis
by creating an immunosuppressive environment. We hypothesized that incorporation of n-3 PUFA suppresses activation of macrophage antimycobacterial responses and favors bacterial growth, in part, by modulating the IFNΞ³-mediated signaling pathway.. The fatty acid composition of macrophage membranes was modified significantly by DHA treatment. DHA-treated macrophages were less effective in controlling intracellular mycobacteria and showed impaired oxidative metabolism and reduced phagolysosome maturation. Incorporation of DHA resulted in defective macrophage activation, as characterized by reduced production of pro-inflammatory cytokines (TNFΞ±, IL-6 and MCP-1), and lower expression of co-stimulatory molecules (CD40 and CD86). DHA treatment impaired STAT1 phosphorylation and colocalization of the IFNΞ³ receptor with lipid rafts, without affecting surface expression of IFNΞ³ receptor. in response to activation by IFNΞ³, by modulation of IFNΞ³ receptor signaling and function, suggesting that n-3 PUFA-enriched diets may have a detrimental effect on host immunity to tuberculosis
Alteration of EGFR Spatiotemporal Dynamics Suppresses Signal Transduction
The epidermal growth factor receptor (EGFR), which regulates cell growth and survival, is integral to colon tumorigenesis. Lipid rafts play a role in regulating EGFR signaling, and docosahexaenoic acid (DHA) is known to perturb membrane domain organization through changes in lipid rafts. Therefore, we investigated the mechanistic link between EGFR function and DHA. Membrane incorporation of DHA into immortalized colonocytes altered the lateral organization of EGFR. DHA additionally increased EGFR phosphorylation but paradoxically suppressed downstream signaling. Assessment of the EGFR-Ras-ERK1/2 signaling cascade identified Ras GTP binding as the locus of the DHA-induced disruption of signal transduction. DHA also antagonized EGFR signaling capacity by increasing receptor internalization and degradation. DHA suppressed cell proliferation in an EGFR-dependent manner, but cell proliferation could be partially rescued by expression of constitutively active Ras. Feeding chronically-inflamed, carcinogen-injected C57BL/6 mice a fish oil containing diet enriched in DHA recapitulated the effects on the EGFR signaling axis observed in cell culture and additionally suppressed tumor formation. We conclude that DHA-induced alteration in both the lateral and subcellular localization of EGFR culminates in the suppression of EGFR downstream signal transduction, which has implications for the molecular basis of colon cancer prevention by DHA
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