Golexanolone improves fatigue, motor incoordination and gait and memory in rats with bile duct ligation

\ua9 2023 The Authors. Liver International published by John Wiley & Sons Ltd.Background and Aims: Many patients with the chronic cholestatic liver disease primary biliary cholangitis (PBC) show fatigue and cognitive impairment that reduces their quality of life. Likewise, rats with bile duct ligation (BDL) are a model of cholestatic liver disease. Current PBC treatments do not improve symptomatic alterations such as fatigue or cognitive impairment and new, more effective treatments are therefore required. Golexanolone reduces the potentiation of GABAA receptors activation by neurosteroids. Golexanolone reduces peripheral inflammation and neuroinflammation and improves cognitive and motor function in rats with chronic hyperammonemia. The aims of the present study were to assess if golexanolone treatment improves fatigue and cognitive and motor function in cholestatic BDL rats and if this is associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. Methods: Rats were subjected to bile duct ligation. One week after surgery, oral golexanolone was administered daily to BDL and sham-operated controls. Fatigue was analysed in the treadmill, motor coordination in the motorater, locomotor gait in the Catwalk, and short-term memory in the Y-maze. We also analysed peripheral inflammation, neuroinflammation, and GABAergic neurotransmission markers by immunohistochemistry and Western blot. Results: BDL induces fatigue, impairs memory and motor coordination, and alters locomotor gait in cholestatic rats. Golexanolone improves these alterations, and this was associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. Conclusion: Golexanolone may have beneficial effects to treat fatigue, and motor and cognitive impairment in patients with the chronic cholestatic liver disease PBC

Dust emission in early-type galaxies: The mid-infrared view

We present mid-infrared (MIR) maps for a sample of 18 early-type galaxies observed at 4.5, 6.7 and 15 microns with the ISOCAM instrument on board the ISO satellite with a 6'' spatial resolution. We model the Spectral Energy Distribution (SED) of these galaxies using the stellar evolutionary synthesis model PEGASE and we derive the MIR excess over the stellar component. We then explore the nature of this excess in terms of dust and Polycyclic Aromatic Hydrocarbon molecules (PAHs). We find that out of 18 galaxies, 10 show excess at 6.7 microns (due to the presence of PAH features) and 14 show excess at 15 microns (due to the presence of warm dust). In two galaxies, where a more complete wavelength coverage exists, an excess around 9.7 microns is seen (presumably due to silicate dust emission), while two other galaxies are totally devoid of dust. We also examine the morphology of the galaxies in these wavelengths by plotting the azimuthally averaged radial profiles as well as the MIR color profiles. We find that for the majority of the galaxies the 4.5 micron emission is well described by a de Vaucouleurs profile. The 6.7 and 15 micron emission is smoothly distributed throughout the galaxy while only a few galaxies show MIR emission which is more concentrated close to the center. Two dwarf galaxies in our sample show patchy distributions of the MIR emission while two other galaxies show edge-on disks. With color-color diagrams we delineate the regions occupied by late-type and early-type galaxies. Finally we show that the MIR excess found in strong radio galaxies like NGC 4486 (M87) can be explained by synchrotron emission.Comment: 12 pages, 19 reduced figures (JPG), Accepted for publication by A&A. A paper with full resolution figures can be found at: http://www.astro.noa.gr/~xilouris/iso/paper.pd

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Biosynthesis of Long Chain Alkyl Diols and Long Chain Alkenols in Nannochloropsis spp. (Eustigmatophyceae)

We investigated potential biosynthetic pathways of long chain alkenols (LCAs), long chain alkyl diols (LCDs), and long chain hydroxy fatty acids (LCHFAs) in Nannochloropsis oceanica and Nannochloropsis gaditana, by combining culturing experiments with genomic and transcriptomic analyses. Incubation of Nannochloropsis spp. in the dark for 1 week led to significant increases in the cellular concentrations of LCAs and LCDs in both species. Consistently, 13C-labelled substrate experiments confirmed that both LCA and LCD were actively produced in the dark from C14-18 fatty acids by either condensation or elongation/hydroxylation, although no enzymatic evidence was found for the former pathway. Nannochloropsis spp. did, however, contain (i) multiple polyketide synthases (PKSs) including one type (PKS-Clade II) that might catalyze incomplete fatty acid elongations leading to the formation of 3-OH-fatty acids, (ii) 3-hydroxyacyl dehydratases (HADs), which can possibly form Δ2/Δ3 monounsaturated fatty acids, and (iii) fatty acid elongases (FAEs) that could elongate 3-OH-fatty acids and Δ2/Δ3 monounsaturated fatty acids to longer products. The enzymes responsible for reduction of the long chain fatty acids to LCDs and LCAs are, however, unclear. A putative wax ester synthase/acyl coenzyme A (acyl-CoA): diacylglycerol acyltransferase is likely to be involved in the esterification of LCAs and LCDs in the cell wall. Our data thus provide useful insights in predicting the biosynthetic pathways of LCAs and LCDs in phytoplankton suggesting a key role of FAE and PKS enzymes

Phenotypic plasticity of European larch radial growth and wood density along a‐1,000 m elevational gradient

Phenotypic plasticity is a key mechanism for sedentary long-living species to adjust to changing environment. Here, we use mature Larix decidua tree-ring variables collected along an elevational transect in the French Alps to characterize the range of individual plastic responses to temperature. Stem cores from 821 mature Larix decidua trees have been collected from four plots distributed along a 1,000-m elevational gradient in a natural forest to build up individual linear reaction norms of tree-ring microdensity traits to temperature. The sign, magnitude and spread of variations of the slopes of the individual reaction norms were used to characterize variation of phenotypic plasticity among plots and traits. Results showed a large range of phenotypic plasticity (with positive and negative slopes) at each elevational plot and for each tree-ring variable. Overall, phenotypic plasticity tends to be larger but positive at higher elevation, negative at the warmer lower sites, and more variable in the center of the elevation distribution. Individual inter-ring reaction norm is a valuable tool to retrospectively characterize phenotypic plasticity of mature forest trees. This approach applied to Larix decidua tree-ring micro-density traits along an elevation gradient showed the existence of large inter-individual variations that could support local adaptation to a fast-changing climate.Estación Experimental Agropecuaria BarilocheFil: Escobar Sandoval, Margarita. Institut National de la Recherche Agronomique (INRA); FranciaFil: Pâques, Luc. Institut National de la Recherche Agronomique (INRA); FranciaFil: Fonti, Patrick. Swiss Federal Institute for Forest Snow and Landscape Research; SuizaFil: Martinez Meier, Alejandro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área de Recursos Forestales. Grupo de Ecología Forestal; ArgentinaFil: Rozenberg, Philippe. Institut National de la Recherche Agronomique (INRA); Franci