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At least 937 records · Page 52

Oxidized low-density lipoprotein-induced periodontal inflammation is associated with the up-regulation of cyclooxygenase-2 and microsomal prostaglandin synthase 1 in human gingival epithelial cells

Highlights: {yields} OxLDL-induced responses in human gingival epithelial cells were studied. {yields} OxLDL enhanced the production of IL-8, IL-1{beta} and PGE{sub 2} in Ca9-22 cells. {yields} An NF-{kappa}B inhibitor suppressed the expression of COX-2 and mPGES1 induced by oxLDL. {yields} Unlike the case in macrophages, oxLDL did not increase the CD36 level. -- Abstract: Periodontitis is characterized by chronic gingival tissue inflammation, and inflammatory mediators such as IL-8 and prostaglandin E{sub 2} (PGE{sub 2}) are associated with disease progression. Previously we showed that oxidatively modified low-density lipoprotein (oxLDL) was present in gingival crevicular fluid. In this study, the role of oxLDL in the gingival epithelial cell inflammatory response was further investigated using Ca9-22 cells and primary human oral keratinocytes (HOK). Treatment of Ca9-22 cells and HOK with oxLDL induced an up-regulation of IL-8 and the PGE{sub 2}-producing enzymes, cyclooxygenase-2 and microsomal PGE{sub 2} synthase-1. These responses induced by oxLDL were significantly suppressed by a nuclear factor-kappa B (NF-{kappa}B) inhibitor. However, unlike the result in macrophages, oxLDL did not lead to an increase in CD36 expression in these two cells. These results suggest that oxLDL elicits gingival epithelial cell inflammatory responses through an activation of the NF-{kappa}B pathway. These data suggest a mechanistic link between periodontal disease and lipid metabolism-related disorders, including atherosclerosis.

60 APPLIED LIFE SCIENCES↗

High temperature conductivity of potassium-beta(double prime)-alumina

Potassium beta(double prime)-alumina (BDPA) single crystals have been reported by several groups to leave higher ionic conductivity than sodium BDPA crystals at room temperature, and similar conductivities are obtained at temperatures up to 600-700 K. Potassium BDPA ceramics have been reported to have significantly poorer conductivities than those of sodium BDPA ceramics, but conductivity measurements at temperatures above 625 K have not been reported. In this study, K(+)-BDPA ceramics were prepared from Na(+)-BDPA ceramic using a modified version of the exchange reaction with KCl vapor reported by Crosbie and Tennenhouse (1982), and the conductivity has been measured in K vapor at temperatures up to 1223 K, using the method of Cole et al. (1979). The results indicate reasonable agreement with earlier data on K(+)-BDPA ceramic measured in a liquid K cell, but show that the K(+)-BDPA ceramic's conductivity approaches that of Na(+)-BDPA ceramic at higher temperatures, being within a factor of four at 700 K and 60 percent of the conductivity of Na(+)-BDPA at T over 1000 K. Both four-probe dc conductivity and four probe ac impedance measurements were used to characterize the conductivity. A rather abrupt change in the grain boundary resistance suggesting a possible phase change in the intergranular material, potassium aluminate, is seen in the ac impedance behavior.

Williams, R. M.↗

THE {sup 12}C + {sup 12}C REACTION AND THE IMPACT ON NUCLEOSYNTHESIS IN MASSIVE STARS

Despite much effort in the past decades, the C-burning reaction rate is uncertain by several orders of magnitude, and the relative strength between the different channels {sup 12}C({sup 12}C, {alpha}){sup 20}Ne, {sup 12}C({sup 12}C, p){sup 23}Na, and {sup 12}C({sup 12}C, n){sup 23}Mg is poorly determined. Additionally, in C-burning conditions a high {sup 12}C+{sup 12}C rate may lead to lower central C-burning temperatures and to {sup 13}C({alpha}, n){sup 16}O emerging as a more dominant neutron source than {sup 22}Ne({alpha}, n){sup 25}Mg, increasing significantly the s-process production. This is due to the chain {sup 12}C(p, {gamma}){sup 13}N followed by {sup 13}N({beta} +){sup 13}C, where the photodisintegration reverse channel {sup 13}N({gamma}, p){sup 12}C is strongly decreasing with increasing temperature. Presented here is the impact of the {sup 12}C+{sup 12}C reaction uncertainties on the s-process and on explosive p-process nucleosynthesis in massive stars, including also fast rotating massive stars at low metallicity. Using various {sup 12}C+{sup 12}C rates, in particular an upper and lower rate limit of {approx}50,000 higher and {approx}20 lower than the standard rate at 5 Multiplication-Sign 10{sup 8} K, five 25 M {sub Sun} stellar models are calculated. The enhanced s-process signature due to {sup 13}C({alpha}, n){sup 16}O activation is considered, taking into account the impact of the uncertainty of all three C-burning reaction branches. Consequently, we show that the p-process abundances have an average production factor increased up to about a factor of eight compared with the standard case, efficiently producing the elusive Mo and Ru proton-rich isotopes. We also show that an s-process being driven by {sup 13}C({alpha}, n){sup 16}O is a secondary process, even though the abundance of {sup 13}C does not depend on the initial metal content. Finally, implications for the Sr-peak elements inventory in the solar system and at low metallicity are discussed.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

The Merging Galaxy Cluster A520 - A Broken-Up Cool Core, A Dark Subcluster, and an X-Ray Channel

We present results from a deep Chandra X-ray observation of a merging galaxy cluster A520. A high-resolution gas temperature map reveals a long trail of dense, cool clumpsapparently the fragments of a cool core that has been stripped from the infalling subcluster by ram pressure. The clumps should still be connected by the stretched magnetic field lines. The observed temperature variations imply that thermal conductivity is suppressed by a factor greater than 100 across the presumed direction of the magnetic field (as found in other clusters), and is also suppressed along the field lines by a factor of several. Two massive clumps in the periphery of A520, visible in the weak-lensing mass map and the X-ray image, have apparently been completely stripped of gas during the merger, but then re-accreted the surrounding high-entropy gas upon exit from the cluster. The mass clump that hosted the stripped cool core is also re-accreting hotter gas. An X-ray hydrostatic mass estimate for the clump that has the simplest geometry agrees with the lensing mass. Its current gas mass to total mass ratio is very low, 1.5 percent to 3 percent, which makes it a "dark subcluster." We also found a curious low X-ray brightness channel (likely a low-density sheet in projection) going across the cluster along the direction of an apparent secondary merger. The channel may be caused by plasma depletion in a region of an amplified magnetic field (with plasma Beta approximately equal to 10-20). The shock in A520 will be studied in a separate paper.

galaxies: clusters: individual (A520) – intergal↗

First NuSTAR Observations of the BL Lac-Type Blazar PKS 2155-304: Constraints on the Jet Content and Distribution of Radiating Particles

We report the first hard X-ray observations with NuSTAR of the BL Lac-type blazar PKS2155-304, augmented with soft X-ray data from XMM-Newton and gamma-ray data from the Fermi Large Area Telescope, obtained in 2013April when the source was in a very low flux state. A joint NuSTAR and XMM spectrum, covering the energy range 0.5-60 keV, is best described by a model consisting of a log-parabola component with curvature Beta = -0.3(+0.2 -0.1) and a (local) photon index 3.04 +/- 0.15 at photon energy of 2 keV, and a hard power-law tail with photon index 2.2 +/- 0.4. The hard X-ray tail can be smoothly joined to the quasi-simultaneous gamma-ray spectrum by a synchrotron self-Compton component produced by an electron distribution with index p 2.2. Assuming that the power-law electron distribution extends down to gamma (sub min) = 1 and that there is one proton per electron, an unrealistically high total jet power of Lp approximately 10 (exp 47) erg s(sub -1) is inferred. This can be reduced by two orders of magnitude either by considering a significant presence of electron-positron pairs with lepton-to-proton ratio n(sub e+e-/n(sub p) approx. 30, or by introducing an additional, low-energy break in the electron energy distribution at the electron Lorentz factor gamma br1 approx. 100. In either case, the jet composition is expected to be strongly matter-dominated

gamma ray↗

Competitive fragmentation pathways of acetic acid dimer explored by synchrotron VUV photoionization mass spectrometry and electronic structure calculations

In present study, photoionization and dissociation of acetic acid dimers have been studied with the synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. Besides the intense signal corresponding to protonated cluster ions (CH{sub 3}COOH){sub n}{center_dot}H{sup +}, the feature related to the fragment ions (CH{sub 3}COOH)H{sup +}{center_dot}COO (105 amu) via {beta}-carbon-carbon bond cleavage is observed. By scanning photoionization efficiency spectra, appearance energies of the fragments (CH{sub 3}COOH){center_dot}H{sup +} and (CH{sub 3}COOH)H{sup +}{center_dot}COO are obtained. With the aid of theoretical calculations, seven fragmentation channels of acetic acid dimer cations were discussed, where five cation isomers of acetic acid dimer are involved. While four of them are found to generate the protonated species, only one of them can dissociate into a C-C bond cleavage product (CH{sub 3}COOH)H{sup +}{center_dot}COO. After surmounting the methyl hydrogen-transfer barrier 10.84 {+-} 0.05 eV, the opening of dissociative channel to produce ions (CH{sub 3}COOH){sup +} becomes the most competitive path. When photon energy increases to 12.4 eV, we also found dimer cations can be fragmented and generate new cations (CH{sub 3}COOH){center_dot}CH{sub 3}CO{sup +}. Kinetics, thermodynamics, and entropy factors for these competitive dissociation pathways are discussed. The present report provides a clear picture of the photoionization and dissociation processes of the acetic acid dimer in the range of the photon energy 9-15 eV.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Structure of the minor pseudopilin XcpW from the Pseudomonas aeruginosa type II secretion system

Pseudomonas aeruginosa utilizes the type II secretion machinery to transport virulence factors through the outer membrane into the extracellular space. Five proteins in the type II secretion system share sequence homology with pilin subunits of type IV pili and are called the pseudopilins. The major pseudopilin X{sub cp}T{sub G} assembles into an intraperiplasmic pilus and is thought to act in a piston-like manner to push substrates through an outer membrane secretin. The other four minor pseudopilins, X{sub cp}U{sub H}, X{sub cp}V{sub I}, X{sub cp}W{sub J} and X{sub cp}X{sub K}, play less well defined roles in pseudopilus formation. It was recently discovered that these four minor pseudopilins form a quaternary complex that is presumed to initiate the formation of the pseudopilus and to localize to its tip. Here, the structure of X{sub cp}W{sub J} was refined to 1.85 {angstrom} resolution. The structure revealed the type IVa pilin fold with an embellished variable antiparallel {beta}-sheet as also found in the X{sub cp}W{sub J} homologue enterotoxigenic Escherichia coli G{sub sp}J{sub W} and the X{sub cp}U{sub H} homologue Vibrio cholerae E{sub ps}U{sub H}. It is proposed that the exposed surface of this sheet may cradle the long N-terminal 1 helix of another pseudopilin. The final 31 amino acids of the X{sub cp}W{sub J} structure are instrinsically disordered. Deletion of this unstructured region of X{sub cp}W{sub J} did not prevent type II secretion in vivo.

59 BASIC BIOLOGICAL SCIENCES↗

Uridine adenosine tetraphosphate (Up{sub 4}A) is a strong inductor of smooth muscle cell migration via activation of the P2Y{sub 2} receptor and cross-communication to the PDGF receptor

Highlights: Black-Right-Pointing-Pointer Up{sub 4}A induces VSMC migration. Black-Right-Pointing-Pointer VSMC migration towards Up{sub 4}A involves P2Y{sub 2} activation. Black-Right-Pointing-Pointer Up{sub 4}A-induced VSMC migration is OPN-dependent. Black-Right-Pointing-Pointer Activation of ERK1/2 pathway is necessary for VSMC migration towards Up{sub 4}A. Black-Right-Pointing-Pointer Up{sub 4}A-directed VSMC migration cross-communicates with the PDGFR. -- Abstract: The recently discovered dinucleotide uridine adenosine tetraphosphate (Up{sub 4}A) was found in human plasma and characterized as endothelium-derived vasoconstrictive factor (EDCF). A further study revealed a positive correlation between Up{sub 4}A and vascular smooth muscle cell (VSMC) proliferation. Due to the dominant role of migration in the formation of atherosclerotic lesions our aim was to investigate the migration stimulating potential of Up{sub 4}A. Indeed, we found a strong chemoattractant effect of Up{sub 4}A on VSMC by using a modified Boyden chamber. This migration dramatically depends on osteopontin secretion (OPN) revealed by the reduction of the migration signal down to 23% during simultaneous incubation with an OPN-blocking antibody. Due to inhibitory patterns using specific and unspecific purinoreceptor inhibitors, Up{sub 4}A mediates it's migratory signal mainly via the P2Y{sub 2}. The signaling behind the receptor was investigated with luminex technique and revealed an activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. By use of the specific PDGF receptor (PDGFR) inhibitor AG1296 and siRNA technique against PDGFR-{beta} we found a strongly reduced migration signal after Up{sub 4}A stimulation in the PDGFR-{beta} knockdown cells compared to control cells. In this study, we present substantiate data that Up{sub 4}A exhibits migration stimulating potential probably involving the signaling cascade of MEK1 and ERK1/2 as well as the matrix protein OPN. We further suggest that the initiation of the migration process occurs predominant through direct activation of the P2Y{sub 2} by Up{sub 4}A and via transactivation of the PDGFR.

60 APPLIED LIFE SCIENCES↗

Radioactivity and thermalization in the ejecta of compact object mergers and their impact on kilonova light curves

One promising electromagnetic signature of compact object mergers are kilonovae: approximately isotropic radioactively powered transients that peak days to weeks post-merger. Key uncertainties in kilonova modeling include the emission profiles of the radioactive decay products—non-thermal β-particles, α-particles, fission fragments, and γ-rays—and the efficiency with which their kinetic energy is absorbed by the ejecta. The radioactive energy emitted, along with its thermalization efficiency, sets the luminosity budget and is therefore crucial for predicting kilonova light curves. We outline uncertainties in the radioactivity, describe the processes by which the decay products transfer energy to the ejecta, and calculate time-dependent thermalization efficiencies for each particle type. We determine the net thermalization efficiency and explore its dependence on r-process yields—in particular, the production of α-decaying translead nuclei—and on ejecta mass, velocity, and magnetic fields. We incorporate our results into detailed radiation transport simulations, and calculate updated kilonova light curve predictions. Thermalization effects reduce kilonova luminosities by a factor of roughly 2 at peak, and by an order of magnitude at later times (15 days or more after explosion). We present analytic fits to time-dependent thermalization efficiencies, which can be used to improve light curve models. We revisit the putative kilonova that accompanied gamma-ray burst 130603B, and estimate the mass ejected in that event. We find later time kilonova light curves can be significantly impacted by α-decay from translead isotopes; data at these times may therefore be diagnostic of ejecta abundances.

79 ASTRONOMY AND ASTROPHYSICS↗

SPATIALLY RESOLVED HST GRISM SPECTROSCOPY OF A LENSED EMISSION LINE GALAXY AT z {approx} 1

We take advantage of gravitational lensing amplification by A1689 (z 0.187) to undertake the first space-based census of emission line galaxies (ELGs) in the field of a massive lensing cluster. Forty-three ELGs are identified to a flux of i{sub 775} = 27.3 via slitless grism spectroscopy. One ELG (at z = 0.7895) is very bright owing to lensing magnification by a factor of Almost-Equal-To 4.5. Several Balmer emission lines (ELs) detected from ground-based follow-up spectroscopy signal the onset of a major starburst for this low-mass galaxy (M{sub *} Almost-Equal-To 2 Multiplication-Sign 10{sup 9} M{sub Sun }) with a high specific star formation rate ( Almost-Equal-To 20 Gyr{sup -1}). From the blue ELs we measure a gas-phase oxygen abundance consistent with solar (12+log(O/H) = 8.8 {+-} 0.2). We break the continuous line-emitting region of this giant arc into seven {approx}1 kpc bins (intrinsic size) and measure a variety of metallicity-dependent line ratios. A weak trend of increasing metal fraction is seen toward the dynamical center of the galaxy. Interestingly, the metal line ratios in a region offset from the center by {approx}1 kpc have a placement on the blue H II region excitation diagram with f ([O III])/f (H{beta}) and f ([Ne III])/f (H{beta}) that can be fitted by an active galactic nucleus (AGN). This asymmetrical AGN-like behavior is interpreted as a product of shocks in the direction of the galaxy's extended tail, possibly instigated by a recent galaxy interaction.

79 ASTRONOMY AND ASTROPHYSICS↗

Enhanced antineutrino emission from 𝛽 decay in core-collapse supernovae with self-consistent weak decay rates

Nuclear weak-interaction rates are known to exert a prominent effect in the late stages of stellar collapse. Despite their importance, most studies to date on core-collapse supernovae (CCSNe) have focused primarily on the effects of electron captures, neglecting 𝛽 decay contributions. In this work, we present the first CCSNe simulation incorporating global 𝛽 decay rates from a microscopic theory. These are enabled by a large-scale evaluation of both electron capture and 𝛽 decay rates, obtained self-consistently utilizing the relativistic energy density functional theory and finite-temperature quasiparticle random-phase approximation. Including 𝛽 decay leads to a dramatic enhancement of the pre-bounce antineutrino signal as the antineutrino emissivity increases by more than two orders of magnitude and the luminosity by a factor of 50 relative to thermal emission alone, while the average antineutrino energy increases by over 1 MeV. Furthermore, it is expected that these new rates could help us constrain the model uncertainties related to weak-interaction processes, improving the prediction of antineutrino signal during the final stages of stellar death.

Beta decay↗

Stellar occultation measurements of atmospheric ozone and chlorine from OAO3

The Princeton University telescope on the Orbiting Astronomical Observatory 3 was used for occultation measurements of upper-atmospheric species. The target star, Beta Cen, and observing date were selected so that the line of sight grazed earth's limb at local midnight. Observations at 2580, 2825, 2997, 3100, and 3428 A produced ozone absorption data of high statistical accuracy between 48-km and 114-km tangent altitude. Near-exponential density profiles are obtained up to 85 km. Near 100 km, a significant density excess above the extrapolated low-altitude profile is observed. Near-equatorial observations at altitudes up to approximately 75 km agree well with theoretical calculations. Ozone densities measured at 6.5 to 12.5 deg S latitude above approximately 75 km exceed the theoretical calculations and are not understood at the present time. A search for the 1188-A chlorine line in the 1187-A O2 absorption feature was carried out at tangent altitudes of 96-116 km. An upper limit of 3 ppb to the atomic chlorine mixing ratio at 106 km is found. This upper limit exceeds the expected value for atomic chlorine by a factor of approximately 2.5.

Riegler, G. R.↗

Sustainable production of radionuclidically pure antimony-119

Background Radiopharmaceutical therapy (RPT) uses radionuclides that decay via one of three therapeutically relevant decay modes (alpha, beta, and internal conversion (IC) / Auger electron (AE) emission) to deliver short range, highly damaging radiation inside of diseased cells, maintaining localized dose distribution and sparing healthy cells. Antimony-119 ( 119 Sb, t 1/2 = 38.19 h, EC = 100%) is one such IC/AE emitting radionuclide, previously limited to in silico computational investigation due to barriers in production, chemical separation, and chelation. A theranostic (therapeutic/diagnostic) pair can be formed with 119 Sb’s radioisotopic imaging analogue 117 Sb (t 1/2 = 2.80 h, E γ = 158.6 keV, I γ = 85.9%, β + = 262.4 keV, I β+ = 1.81%). Results Within, we report techniques for sustainable and cost-effective production of pre-clinical quality and quantity, radionuclidically pure 119 Sb and 117 Sb, novel low energy photon measurement techniques for 119 Sb activity determination, and physical yields for various tin target isotopic enrichments and thicknesses using (p, n) and (d, n) nuclear reactions. Additionally, we present a two-column separation providing a radioantimony yield of 73.1% ± 6.9% (N = 3) and tin separation factor of (6.8 ± 5.5) x 10 5 (N = 3). Apparent molar activity measurements for deuteron produced 117 Sb using the chelator TREN-CAM were measured at 42.4 ± 25 MBq 117 Sb/µmol (1.14 ± 0.68 mCi/µmol), and we recovered enriched 119 Sn target material at a recycling efficiency of 80.2% ± 5.5% (N = 6) with losses of 11.6 mg ± 0.8 mg (N = 6) per production. Conclusion We report significant steps in overcoming barriers in 119 Sb production, chemical isolation and purification, enriched target material recycling, and chelation, helping promote accessibility and application of this promising therapeutic radionuclide. We describe a method for 119 Sb activity measurement using its low energy gamma (23.87 keV), negating the need for attenuation correction. Finally, we report the largest yet-measured 119 Sb production yields using proton and deuteron irradiation of natural and enriched targets and radioisotopic purity > 99.8% at end of purification.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Heat load measurements for the PIP-II pHB650 cryomodule

This study presents a brief overview of the 1st and 2nd phases and an in-depth analysis of the 3rd phase heat load testing performed on the pHB650 (prototype High Beta 650 MHz) cryomodule at PIP2IT (PIP-II Injector Test Facility), with a focus on both the results and the methodological advancements that have improved testing efficiency and accuracy. A key challenge identified in the testing campaign is the higher-than-expected heat loads observed in the first PIP-II (Proton Improvement Plan II) prototype cryomodules (pSSR1 and pHB650) tested at PIP2IT. Elevated heat loads are concerning given the fixed capacity of the PIP-II cryoplant that is currently being installed at Fermilab. However, understanding the sources of these elevated heat loads offers a critical opportunity to implement effective heat load mitigations on upcoming PIP-II cryomodules to stay within the available capacity of the PIP-II cryoplant. The study includes a summary of test results, descriptions of measurement procedures, and key observations on parameters directly and indirectly related to heat load measurements. Direct observations include measured heat loads and the effectiveness of JT heat exchanger under varying conditions, while indirect observation analyze factors such as the temperature distribution on the two-phase pipe and relief piping under varying conditions. Thermal acoustic oscillations (TAO) were identified during testing, which was mitigated by replacing the original G10 stem with a stainless steel stem equipped with wipers for the cryomodule cooldown valve. A major innovation during pHB650 Phase 3 testing was the development of an automated Python script to streamline data acquisition, analysis, and reporting of heat load results. This script automatically retrieved data from ACNET (Accelerator Control Network), performed heat load calculations, and generated detailed reports featuring plots and tables. This advancement significantly reduced manual labor and enhanced the thoroughness of data analysis compared to earlier campaigns. The heat load test reports were promptly uploaded to the electronic logbook shortly after each test, enabling rapid feedback and collaboration between the SRF and cryogenic teams. The heat load measurements included various components: HTTS (high-temperature thermal shield), LTTS (low-temperature thermal shield), 2K isothermal and non-isothermal heat loads. Results were recorded both within the cryomodule and between the bayonet can supply and return. Measurements were conducted under different operating conditions such as "standard", "linac", and "simulated dynamic". Additionally, HTTS and LTTS heat loads were calculated in real time, allowing for the tracking of thermal stability and identification of changes during testing, both in steady-state and transient conditions. The results of this testing campaign not only provide valuable insights into the performance of the pHB650 cryomodule but also highlight best practices and lessons learned that will inform future cryomodule testing at PIP2IT. These include adopting automated tools for data analysis, refining real-time measurement capabilities, and emphasizing detailed pre-test planning. The framework established in this campaign aims to set an improved standard for cryomodule testing and heat load reporting in future cryomodule test campaigns.

Porwisiak, D. [Fermilab; Wroclaw Tech. U.]↗

SUB-ALFVENIC NON-IDEAL MAGNETOHYDRODYNAMIC TURBULENCE SIMULATIONS WITH AMBIPOLAR DIFFUSION. III. IMPLICATIONS FOR OBSERVATIONS AND TURBULENT ENHANCEMENT

Ambipolar diffusion (AD) is believed to be a crucial process for redistributing magnetic flux in the dense molecular gas that occurs in regions of star formation. We carry out numerical simulations of this process in regions of low ionization using the heavy-ion approximation. The simulations are for regions of strong field (plasma {beta} = 0.1) and mildly supersonic turbulence (M=3, corresponding to an Alfven Mach number of 0.67). The velocity power spectrum of the neutral gas changes from an Iroshnikov-Kraichnan spectrum in the case of ideal MHD to a Burgers spectrum in the case of a shock-dominated hydrodynamic system. The magnetic power spectrum shows a similar behavior. We use a one-dimensional radiative transfer code to post-process our simulation results; the simulated emission from the CS J = 2-1 and H{sup 13}CO{sup +} J = 1-0 lines shows that the effects of AD are observable in principle. Linewidths of ions are observed to be less than those of neutrals, and we confirm previous suggestions that this is due to AD. We show that AD is unlikely to affect the Chandrasekhar-Fermi method for inferring field strengths unless the AD is stronger than generally observed. Finally, we present a study of the enhancement of AD by turbulence, finding that AD is accelerated by factor 2-4.5 for non-self-gravitating systems with the level of turbulence we consider.

79 ASTRONOMY AND ASTROPHYSICS↗

Increased urine acylcarnitines in diabetic ApoE-/- mice: Hydroxytetradecadienoylcarnitine (C14:2-OH) reflects diabetic nephropathy in a context of hyperlipidemia

Hyperlipidemia is a risk factor for initiation and progression of diabetic nephropathy but the metabolic pathways altered in the diabetic kidney in a context of hyperlipidemia remain incompletely described. Assuming that changes in urine composition reflect the alteration of renal metabolism and function, we analyzed the urine metabolite composition of diabetic (streptozotocin-treatment) and control (non diabetic) ApoE−/− mice fed a high cholesterol diet using targeted quantitative metabolomics. Urine metabolome was also compared to the plasma metabolome of the same animals. As previously shown, urine albuminuria/urine creatinine ratio (uACR) and glomerular area and plasma lipids (cholesterol, triglycerides) were more elevated in diabetic mice compared to control. After adjustment to urine creatinine, the abundance of 52 urine metabolites was significantly different in diabetic mice compared to control. Among them was a unique metabolite, C14:2-OH (3-hydroxytetradecadienoylcarnitine) that, in diabetic mice, was positively and significantly correlated with uACR, glomerular hypertrophy, blood glucose and plasma lipids. That metabolite was not detected in plasma. C14:2-OH is a long-chain acylcarnitine reminiscent of altered fatty acid beta oxidation. Other acylcarnitines, particularly the short chains C3-OH, C3-DC, C4:1, C5-DC, C5-M-DC, C5-OH that are reminiscent of altered oxidation of branched and aromatic amino acids were also exclusively detected in urine but were only correlated with plasma lipids. Finally, the renal gene expression of several enzymes involved in fatty acid and/or amino acid oxidation was significantly reduced in diabetic mice compared to control. This included the bifunctional enoyl-CoA hydratase/3-hydroxyacyl-CoA (Ehhadh) that might play a central role in C14:2-OH production. This study indicate that the development of diabetes in a context of hyperlipidemia is associated with a reduced capacity of kidney to oxidize fatty acids and amino acids with the consequence of an elevation of urinary acetylcarnitines including C14:2-OH that specifically reflects diabetic nephropathy.

60 APPLIED LIFE SCIENCES↗

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

NASA Discipline Musculoskeletal↗

Suppression of hepatic stellate cell activation by microRNA-29b

Highlights: {yields} Expression of miR-29b was found to be down-regulated during the activation of hepatic stellate cells in primary culture. {yields} Transfection of a miR-29b precursor markedly attenuated the expression of Col1a1 and Col1a2 mRNAs. {yields} It blunted the increased expression of {alpha}-SMA, DDR2, FN1, ITGB1, and PDGFR-b mRNAs essential for stellate cell activation. {yields} miR-29b overexpression led stellate cells to remain in a quiescent state, as evidenced by their star-like morphology. {yields} miR-29b overexpression suppressed the expression of c-fos mRNA. -- Abstract: MicroRNAs (miRNAs) participate in the regulation of cellular functions including proliferation, apoptosis, and migration. It has been previously shown that the miR-29 family is involved in regulating type I collagen expression by interacting with the 3'UTR of its mRNA. Here, we investigated the roles of miR-29b in the activation of mouse primary-cultured hepatic stellate cells (HSCs), a principal collagen-producing cell in the liver. Expression of miR-29b was found to be down-regulated during HSC activation in primary culture. Transfection of a miR-29b precursor markedly attenuated the expression of Col1a1 and Col1a2 mRNAs and additionally blunted the increased expression of {alpha}-SMA, DDR2, FN1, ITGB1, and PDGFR-{beta}, which are key genes involved in the activation of HSCs. Further, overexpression of miR-29b led HSCs to remain in a quiescent state, as evidenced by their quiescent star-like cell morphology. Although phosphorylation of FAK, ERK, and Akt, and the mRNA expression of c-jun was unaffected, miR-29b overexpression suppressed the expression of c-fos mRNA. These results suggested that miR-29b is involved in the activation of HSCs and could be a candidate molecule for suppressing their activation and consequent liver fibrosis.

60 APPLIED LIFE SCIENCES↗