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Heliospheric plasma turbulence plays a key role in transferring the energy of large-scale magnetic field and plasma flow fluctuations to smaller scales where the energy can be dissipated, ultimately leading to plasma heating. High-quality measurements of electromagnetic fields and electron velocity distributions by the Magnetospheric Multiscale (MMS) mission in Earth's magnetosheath present a unique opportunity to characterize plasma turbulence and to determine the mechanisms responsible for its dissipation. We apply the field-particle correlation technique to a set of twenty MMS magnetosheath intervals to identify the dissipation mechanism and quantify the dissipation rate. It is found that 95% of the intervals have velocity-space signatures of electron Landau damping that are quantitatively consistent with linear kinetic theory for the collisionless damping of kinetic Alfv\'en waves. About 75% of the intervals contain asymmetric signatures, indicating a local imbalance of kinetic Alfv\'en wave energy flux in one direction along the magnetic field than the other. About one third of the intervals have an electron energization rate with the same order-of-magnitude as the estimated turbulent cascade rate, suggesting that electron Landau damping plays a significant, and sometimes dominant, role in the dissipation of the turbulent energy in these magnetosheath intervals., Comment: 26 pages, 8 figures, 2 tables, JGR Space Physics

The importance of the cytochrome P450 (CYP) enzyme family in xenobiotic metabolism, as well as their differential expression and activity in response to a wide range of environmental chemicals and pharmaceuticals, is well documented. The objective of this study was to evaluate the specificity of the branched DNA (bDNA) signal amplification technique for the detection of multiple rat CYPs from hepatocellular RNA. Oligonucleotide probe sets were designed to various chemically inducible rat CYP mRNA transcripts, including CYP1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP3A1/23, and CYP4A2/3. The robustness of the bDNA assay was assessed with the CYP2B1/2-specific probe set, and total RNA was isolated from control and phenobarbital (PB)-treated rats. Analysis of these RNA samples by bDNA signal amplification resulted in a linear quantifiable range of RNA detection that spanned three orders of magnitude (0.1-100 microg of total RNA). The fidelity of the bDNA assay was evaluated within a single assay and between assays where repeated measurements of a single sample were reproduced reliably. The specificity of individual CYP probe sets was evaluated with five typical CYP-inducing chemicals on the expression of specific hepatic CYP mRNA transcripts. Male Sprague-Dawley rats were administered 3-methylcholanthrene, PB, isoniazid, pregnenolone-16alpha-carbonitrile, or clofibric acid to induce transcription of CYP1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP3A1/23, and CYP4A2/3 mRNA, respectively. Analysis of chemical-induced differences in gene expression by bDNA signal amplification indicated that 3-methylcholanthrene induced CYP1A1 and CYP1A2 mRNA levels 670- and 11-fold, respectively; PB induced CYP2B1/2 expression 71-fold; pregnenolone-16alpha-carbonitrile induced CYP3A1/23 expression 34-fold; and clofibric acid induced CYP4A2/3 expression 4.7-fold. Overall, these data support the use of bDNA signal amplification technology as a robust, reproducible, and efficient means of monitoring the differential expression of multiple isoforms of the CYP enzyme family.

The ontogenic and hormonal regulation of a sulfotransferase, SULT1B1, was examined. Hepatic RNA was isolated from rats of various ages from 1 to 90 days. The mRNA for SULT1B1 is low for both sexes until a dramatic increase ( approximately 6-fold) occurs between 15 and 30 days of age in male rats. SULT1B1 expression then decreases to half of the maximal level by 90 days of age. The increase in SULT1B1 mRNA in female rats is less dramatic and occurs between 30 and 45 days of age. SULT1B1 mRNA expression plateaus from 45 to 90 days in female rats. Expression of SULT1B1 mRNA is comparable in adult male and female rats. RNA was isolated from hypophysectomized (HX) animals and HX animals treated with growth hormone [by either male (injection) or female (infusion) pattern], estradiol, progesterone, or testosterone. HX and HX plus growth hormone, or HX plus steroid replacement, did not alter SULT1B1 mRNA expression. Pituitary-intact rats were treated with steroidal compounds dexamethasone (DEX) and pregnenolone-16alpha-carbonitrile (PCN). Both DEX and PCN increased expression of SULT1B1 mRNA in male rats (4- and 3-fold, respectively). However, in female rats, only PCN induced SULT1B1 mRNA (2-fold), whereas DEX did not induce SULT1B1 in female rats. Analysis of SULT1B1 protein expression indicated that only when SULT1B1 mRNA was markedly increased, that is in DEX-treated male rats, was SULT1B1 protein increased. Thus, although adult male and female rats have similar SULT1B1 mRNA expressions, the patterns develop ontogenically differently. SULT1B1 is not regulated by pituitary hormones and DEX induces SULT1B1 protein in male rats.

Our laboratory has previously reported on the ability of 4-hydroxynonenal (4-HNE), a primary product of lipid peroxidation, to inhibit acetaldehyde metabolism in isolated mouse liver mitochondria. The purpose of the present study is to determine whether the co-metabolism of ethanol and 4-HNE compromises the elimination of either substrate in isolated rat hepatocytes. Hepatocytes were isolated and incubated with ethanol and 4-HNE. Ethanol elimination and acetaldehyde accumulation were monitored by gas chromatography, whereas 4-HNE elimination and metabolite accumulation were measured by UV detection and reversed-phase HPLC at 202 nm. In the absence of 4-HNE, hepatocytes metabolized ethanol at an initial rate of 9.4 nmol/min/million cells. Ethanol elimination was moderately inhibited by the presence of 4-HNE. Accumulation of ethanol-derived acetaldehyde was not apparent in incubations with only ethanol. In contrast, in incubations containing both substrates, ethanol-derived acetaldehyde accumulation exceeded that observed in hepatocytes exposed only to ethanol and was proportional to the 4-HNE concentration in the incubations. In all instances, the rate of 4-HNE elimination was not compromised by the presence of ethanol. Accordingly, ethanol metabolism did not alter the oxidative or conjugative metabolism of 4-HNE. However, the reductive metabolism of 4-HNE was affected by the presence of ethanol, wherein accumulation of 1,4-dihydroxy-2-nonene increased2-fold of that observed in incubations with only 4-HNE. To determine further if 4-HNE and ethanol are metabolized through the same metabolic pathways, cells were preincubated with either 4-methylpyrazole or cyanamide to inhibit alcohol dehydrogenase (E.C. 1.1.1.1.) and aldehyde dehydrogenase (E.C. 1.2.1.2.), respectively. Expectantly, 4-methylpyrazole blocked the formation of 1,4-dihydroxy-2-nonene, but had no effect on the rate of 4-HNE elimination. In contrast, cyanamide substantially inhibited the formation of 4-hydroxy-2-nonenoic acid, decreased the rate of 1,4-dihydroxy-2-nonene formation, but did not decrease the elimination rate of 4-HNE. Overall, these results support our previous observation that 4-HNE inhibits acetaldehyde metabolism and establish that ethanol and 4-HNE are metabolized through the same alcohol dehydrogenase- and aldehyde dehydrogenase-mediated pathways. These data continue to suggest that, as a consequence of enhanced lipid peroxidation resulting from chronic ethanol consumption, increased 4-HNE levels could compromise cellular elimination of ethanol-derived acetaldehyde and thus function in the potentiation of alcoholic liver fibrosis.