Spatial variations in aromatic hydrocarbon emission in a dust-rich galaxy.

Dust grains absorb half of the radiation emitted by stars throughout the history of the universe, re-emitting this energy at infrared wavelengths1-3. Polycyclic aromatic hydrocarbons (PAHs) are large organic molecules that trace millimetre-size dust grains and regulate the cooling of interstellar gas within galaxies4,5. Observations of PAH features in very distant galaxies have been difficult owing to the limited sensitivity and wavelength coverage of previous infrared telescopes6,7. Here we present James Webb Space Telescope observations that detect the 3.3 µm PAH feature in a galaxy observed less than 1.5 billion years after the Big Bang. The high equivalent width of the PAH feature indicates that star formation, rather than black hole accretion, dominates infrared emission throughout the galaxy. The light from PAH molecules, hot dust and large dust grains and stars are spatially distinct from one another, leading to order-of-magnitude variations in PAH equivalent width and ratio of PAH to total infrared luminosity across the galaxy. The spatial variations we observe suggest either a physical offset between PAHs and large dust grains or wide variations in the local ultraviolet radiation field. Our observations demonstrate that differences in emission from PAH molecules and large dust grains are a complex result of localized processes within early galaxies.

Modeling Multiphase Heat and Mass Transfer in an Agitated Filter Dryer by Integrating Experiment, Computations, and Analytical Solutions.

The drying of a wet cake consisting of an active pharmaceutical ingredient and solvent in an agitated filter-dryer is a critical and challenging unit operation in the pharmaceutical industry. The complexity of this operation is attributed to the constraints on product quality in terms of its physical properties in addition to the residual solvent content. In this manuscript, a better understanding of the drying mechanism is gained by integrating insights from three-dimensional analytical solutions and computational fluid dynamics simulations into a zero-dimensional model to explain experimental data. The approach provides the time evolution of the mass flow rate of solvent from the wet cake and the center-point temperature of the cake with good accuracy. Further investigation of the zero-dimensional model reveals important parameters such as the mass transfer rate number that predicts whether the process is convection-controlled or diffusion-controlled, and the thermal load of vaporization that estimates the fraction of solvent vaporized per unit time. These parameters can be useful in devising a drying protocol for agitated-filter dryers.

Glucose as a carbon source to synthesize palmitate de novo in the adult rodent brain: Adding to the carbon recycling story in the brain.

While brain glucose metabolism is known to contribute the carbons to support brain saturated and monounsaturated fatty biosynthesis de novo in the developing brains of young rodents, such a contribution to fatty acid biosynthesis in the adult brain is poorly understood. Recent work from the Bazinet laboratory illuminates the role of brain glucose metabolism in providing a carbon source from which palmitic acid is synthesized. In "The Majority of Brain Palmitic Acid is Maintained by Lipogenesis from Dietary Sugars and is Augmented in Offspring fed low Palmitic Acid Levels from Birth", the Bazinet lab demonstrates the importance of glucose as a key contributing source of carbon for brain palmitic synthesis and that a low palmitate diet exacerbates its utilization for brain palmitate synthesis de novo. Further, this impact is found in male mice rather than female mice, which adds an additional layer of importance. Mammals are known to conserve carbon and the brain has the ability to convert a variety of carbon sources to needed molecules, depending on the physiological needs of the brain. Overall, this paper contributes an important missing piece of the puzzle regarding carbon recycling in the brain and is a key piece of evidence that indeed the adult mammalian brain can convert glucose to carbons for use in saturated fatty acid synthesis.

Postmortem Analyses in a Patient With Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): II. Histological, Lipid, and Gene Expression Outcomes in Regional Brain Tissue.

This study has extended previous metabolic measures in postmortem tissues (frontal and parietal lobes, pons, cerebellum, hippocampus, and cerebral cortex) obtained from a 37-year-old male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) who expired from SUDEP (sudden unexplained death in epilepsy). Histopathologic characterization of fixed cortex and hippocampus revealed mild to moderate astrogliosis, especially in white matter. Analysis of total phospholipid mass in all sections of the patient revealed a 61% increase in cortex and 51% decrease in hippocampus as compared to (n = 2-4) approximately age-matched controls. Examination of mass and molar composition of major phospholipid classes showed decreases in phospholipids enriched in myelin, such as phosphatidylserine, sphingomyelin, and ethanolamine plasmalogen. Evaluation of gene expression (RT2 Profiler PCR Arrays, GABA, glutamate; Qiagen) revealed dysregulation in 14/15 GABAA receptor subunits in cerebellum, parietal, and frontal lobes with the most significant downregulation in ∊, θ, ρ1, and ρ2 subunits (7.7-9.9-fold). GABAB receptor subunits were largely unaffected, as were ionotropic glutamate receptors. The metabotropic glutamate receptor 6 was consistently downregulated (maximum 5.9-fold) as was the neurotransmitter transporter (GABA), member 13 (maximum 7.3-fold). For other genes, consistent dysregulation was seen for interleukin 1ß (maximum downregulation 9.9-fold) and synuclein α (maximal upregulation 6.5-fold). Our data provide unique insight into SSADHD brain function, confirming astrogliosis and lipid abnormalities previously observed in the null mouse model while highlighting long-term effects on GABAergic/glutamatergic gene expression in this disorder.

Sterol Carrier Protein-2/Sterol Carrier Protein-x/Fatty Acid Binding Protein-1 Ablation Impacts Response of Brain Endocannabinoid to High-Fat Diet.

Brain endocannabinoids (EC) such as arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) primarily originate from serum arachidonic acid (ARA), whose level is regulated in part by a cytosolic ARA-binding protein, that is, liver fatty acid binding protein-1 (FABP1), not expressed in the brain. Ablation of the Fabp1 gene (LKO) increases brain AEA and 2-AG by decreasing hepatic uptake of ARA to increase serum ARA, thereby increasing ARA availability for uptake by the brain. The brain also expresses sterol carrier protein-2 (SCP-2), which is also a cytosolic ARA-binding protein. To further resolve the role of SCP-2 independent of FABP1, mice ablated in the Scp-2/Scp-x gene (DKO) were crossed with mice ablated in the Fabp1 gene (LKO) mice to generate triple knock out (TKO) mice. TKO impaired the ability of LKO to increase brain AEA and 2-AG. While a high-fat diet (HFD) alone increased brain AEA, TKO impaired this effect. Overall, these TKO-induced blocks were not attributable to altered expression of brain proteins in ARA uptake, AEA/2-AG synthesis, or AEA/2-AG degrading enzymes. Instead, TKO reduced serum levels of free ARA and/or total ARA and thereby decreased ARA availability for uptake to the brain and downstream synthesis of AEA and 2-AG therein. In summary, Scp-2/Scp-x gene ablation in Fabp1 null (LKO) mice antagonized the impact of LKO and HFD on brain ARA and, subsequently, EC levels. Thus, both FABP1 and SCP-2 participate in regulating the EC system in the brain.

Origins Space Telescope: predictions for far-IR spectroscopic surveys.

We illustrate the extraordinary potential of the (far-IR) Origins Survey Spectrometer (OSS) on board the Origins Space Telescope (OST) to address a variety of open issues on the co-evolution of galaxies and AGNs. We present predictions for blind surveys, each of 1000 h, with different mapped areas (a shallow survey covering an area of 10 deg2 and a deep survey of 1 deg2) and two different concepts of the OST/OSS: with a 5.9m telescope (Concept 2, our reference configuration) and with a 9.1 m telescope (Concept 1, previous configuration). In 1000 h, surveys with the reference concept will detect from ~ 1.9 × 106 to ~ 8.7 × 106 lines from ~ 4.8 × 105-2.7 × 106 star-forming galaxies and from ~ 1.4 × 104 to ~ 3.8 × 104 lines from ~ 1.3 × 104-3.5 × 104 AGNs. The shallow survey will detect substantially more sources than the deep one; the advantage of the latter in pushing detections to lower luminosities/higher redshifts turns out to be quite limited. The OST/OSS will reach, in the same observing time, line fluxes more than one order of magnitude fainter than the SPICA/SMI and will cover a much broader redshift range. In particular it will detect tens of thousands of galaxies at z ≥ 5, beyond the reach of that instrument. The polycyclic aromatic hydrocarbons lines are potentially bright enough to allow the detection of hundreds of thousands of star-forming galaxies up to z ~ 8.5, i.e. all the way through the re-ionization epoch. The proposed surveys will allow us to explore the galaxy-AGN co-evolution up to z ~ 5.5 - 6 with very good statistics. OST Concept 1 does not offer significant advantages for the scientific goals presented here.

Scp-2/Scp-x ablation in Fabp1 null mice differentially impacts hepatic endocannabinoid level depending on dietary fat.

Dysregulation of the hepatic endocannabinoid (EC) system and high fat diet (HFD) are associated with non-alcoholic fatty liver disease. Liver cytosol contains high levels of two novel endocannabinoid binding proteins-liver fatty acid binding protein (FABP1) and sterol carrier protein-2 (SCP-2). While Fabp1 gene ablation significantly increases hepatic levels of arachidonic acid (ARA)-containing EC and sex-dependent response to pair-fed high fat diet (HFD), the presence of SCP-2 complicates interpretation. These issues were addressed by ablating Scp-2/Scp-x in Fabp1 null mice (TKO). In control-fed mice, TKO increased hepatic levels of arachidonoylethanolamide (AEA) in both sexes. HFD impacted hepatic EC levels by decreasing AEA in TKO females and decreasing 2-arachidonoyl glycerol (2-AG) in WT of both sexes. Only TKO males on HFD had increased hepatic 2-AG levels. Hepatic ARA levels were decreased in control-fed TKO of both sexes. Changes in hepatic AEA/2-AG levels were not associated with altered amounts of hepatic proteins involved in AEA/2-AG synthesis or degradation. These findings suggested that ablation of the Scp-2/Scp-x gene in Fabp1 null mice exacerbated hepatic EC accumulation and antagonized the impact of HFD on hepatic EC levels-suggesting both proteins play important roles in regulating the hepatic EC system.

Ether lipids and their elusive function in the nervous system: a role for plasmalogens: An Editorial Highlight for 'Reduced muscle strength in ether lipid-deficient mice is accompanied by altered development and function of the neuromuscular junction' on page 569.

In this editorial, we highlight the recent work of Dorninger et al. that demonstrates a reduction in plasmalogens in the motor end plate is associated with a reduction in motor end plate function. This reduction in function is illuminated in reduced muscle function in these mice, corresponding with the reduction in acetylcholine release and in its receptor density observed in these mice.

The blood-brain barrier and protein-mediated fatty acid uptake: role of the blood-brain barrier as a metabolic barrier: An Editorial Comment for 'The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport'.

Read the commented article 'The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport' on page 400.

Comparative effects of high oleic acid vs high mixed saturated fatty acid obesogenic diets upon PUFA metabolism in mice.

Emerging evidence indicates that the fatty acid composition of obesogenic diets influences physiologic outcomes. There are scant data regarding how the content of non-essential fatty acids like monounsaturated fatty acids (MUFA) and saturated fatty acids (SFAs) impact the metabolism of polyunsaturated fatty acids (PUFAs). In this work, we tested the hypothesis that obesogenic diets enriched in oleic acid (OA; 18:1n-9) reduce polyunsaturated fatty acid (PUFA) levels vs an obesogenic diet enriched in SFAs. Adult male mice were fed for eight weeks either (1) a control 16% fat energy (en) diet with 5.7% en OA and 4.4% en SFA, (2) a 50% fat en diet with 33% en OA and 9.9% en SFA, or (3) a 50% en diet with a high SFA diet with 33% en SFA and 9.1% en OA. Dietary levels and intake of linoleic acid (LA; 18:2n-6) and α-linolenic acid (ALA; 18:3n-3) were constant between the experimental groups. Several peripheral organs (liver, heart, kidney, and adipose) were analyzed for lipid composition and oxylipin analysis was performed for liver and adipose. Our data demonstrate that a high OA diet reduced tissue content of LA and ALA (≥30%) in phospholipid and neutral lipid fractions, reduced the content of some LA-derived and ALA-derived oxylipins in liver and adipose, and conversely, elevated hepatic content of PGF2α. In all tissues examined, except for adipose, levels of arachidonic acid (ARA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) were either elevated or unaffected by the obesogenic diets. Our data indicate that the non-essential fatty content of obesogenic diets impacts PUFA content in peripheral tissues and influences the levels of bioactive oxylipins.

Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice.

Female Mice are Resistant to Fabp1 Gene Ablation-Induced Alterations in Brain Endocannabinoid Levels.

Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in the brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing EC, i.e. arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: (1) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; (2) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or (3) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO).

FABP-1 gene ablation impacts brain endocannabinoid system in male mice.

Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids (EC) such as arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). The brain derives most of its ARA from plasma, taking up ARA and transporting it intracellularly via cytosolic fatty acid-binding proteins (FABPs 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP1 is not detectable in the brain but is instead highly expressed in the liver. Therefore, the possibility that FABP1 outside the central nervous system may regulate brain AEA and 2-AG was examined in wild-type (WT) and FABP1 null (LKO) male mice. LKO increased brain levels of AA-containing EC (AEA, 2-AG), correlating with increased free and total ARA in brain and serum. LKO also increased brain levels of non-ARA that contain potentiating endocannabinoids (EC*) such as oleoyl ethanolamide (OEA), PEA, 2-OG, and 2-PG. Concomitantly, LKO decreased serum total ARA-containing EC, but not non-ARA endocannabinoids. LKO did not elicit these changes in the brain EC and EC* as a result of compensatory up-regulation of brain protein levels of enzymes in EC synthesis (NAPEPLD, DAGLα) or cytosolic EC chaperone proteins (FABPs 3, 5, 7, SCP-2, HSP70), or cannabinoid receptors (CB1, TRVP1). These data show for the first time that the non-CNS fatty acid-binding protein FABP1 markedly affected brain levels of both ARA-containing endocannabinoids (AEA, 2-AG) as well as their non-ARA potentiating endocannabinoids. Fatty acid-binding protein-1 (FABP-1) is not detectable in brain but instead is highly expressed in liver. The possibility that FABP1 outside the central nervous system may regulate brain endocannabinoids arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) was examined in wild-type (WT) and FABP-1 null (LKO) male mice. LKO increased brain levels of arachidonic acid-containing endocannabinoids (AEA, 2-AG), correlating with increased free and total arachidonic acid in brain and serum. Read the Editorial Highlight for this article on page 371.