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- Fan, Y., et al.
(author)
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The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice
- 2023
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In: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 8, s. 787-802
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Journal article (peer-reviewed)abstract
- Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis. Faecal metagenomics and serum metabolomics reveal compositional and functional alterations in the gut microbiota of women with anorexia nervosa, and faecal transplants could transfer an anorexia-associated phenotype to germ-free mice.
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- Hort, O., et al.
(author)
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ELI beamlines user oriented high-harmonic beamline
- 2020
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In: Optics InfoBase Conference Papers. - 2162-2701.
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Conference paper (peer-reviewed)abstract
- We present latest progress and experimental capabilities of user-oriented XUV beamline based on high harmonic generation (HHG). The focal length of the HHG was recently extended to 5 meters, upscaling the overall XUV photon flux.
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- Andersson, Linda, 1973, et al.
(author)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Journal article (peer-reviewed)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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- Bibimoune, I., et al.
(author)
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Characterization of defect microstructure in MgRE (RE=Ce, Nd) alloys after processing by high-pressure torsion using positron annihilation spectroscopy and a high resolution X-ray diffraction
- 2023
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In: Physica B: Condensed Matter. - 0921-4526. ; 663
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Journal article (peer-reviewed)abstract
- Two MgRE (RE = Ce, Nd) alloys with ultrafine-grain (UFG) microstructures were prepared by high-pressure torsion (HPT) at room temperature. The in-depth distribution of defects was characterized by Doppler broadening –variable energy positron annihilation spectroscopy (DB-VEPAS). The characteristic S parameter increases in bulk after HPT processing relative to an as-received sample and shows a relative stability between ½ and 10 turns, which suggests a rise in the open volume defect density. However, a theoretical analysis of the S(E) depth profile reveals an increase in the positron diffusion length from ∼115 nm for the as-received state to ∼207 nm after 10 HPT turns. Almost all the open volume defect consisted of dislocations (positron lifetime of τ = 260 ps). The dislocation density deduced from high-resolution X-ray diffraction in the HPT disc radial direction was reasonably homogeneous (around 4–6 × 1014 m−2).
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- Botan, Alexandru, et al.
(author)
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Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions
- 2015
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 119:49, s. 15075-15088
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Journal article (peer-reviewed)abstract
- Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very accurate experimental data, the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR. experiments in terms of the highly structurally sensitive C-H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P-N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files (https://zenodo.org/collection/user-nmrlipids) has become the most extensive publicly available collection of molecular dynamics simulation trajectories of lipid bilayers.
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- Burla, Bo, et al.
(author)
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MS-based lipidomics of human blood plasma : a community-initiated position paper to develop accepted guidelines
- 2018
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In: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 59:10, s. 2001-2017
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Journal article (peer-reviewed)abstract
- Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.
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