Genotype (Germany)

Abstract The impact of the genetic background on the lipidome of yeast strains remains underexplored. This study systematically compares the lipidomes of five commonly used laboratory yeast strains: BY4741, W303, D273-10B, RM11-1a, and CEN.PK2-1c. Shotgun lipidomics reveals significant variations in lipid class and acyl chain composition down to the level of molecular species. Notably, the most abundant lipid class differed between the strains: phosphatidylinositol (PI) lipids are predominant in BY4741, while phosphatidylethanolamine (PE) lipids are in D273. Ergosterol esters, which are the storage form of the major yeast sterol ergosterol, are at higher levels in all strains other than BY4741, correlating with a low gene expression of lipid metabolic enzymes Hmg1 and Are2 in BY4741. Despite these lipidomic differences, transcriptomic analysis did not show significant changes in most genes related to lipid metabolism, suggesting post-transcriptional modifications, protein abundance, and metabolic flux as potential regulatory mechanisms. This study underscores the complexity of lipidome regulation and the need for further investigation into the underlying mechanisms.

Introduction: The stratum corneum (SC) matrix is composed of free fatty acids, cholesterol, and ceramides (CERs), which play a key role in the skin barrier function. Changes in the composition and content of skin lipids will affect the function of the skin barrier. The effect of a glycerol/petrolatum-based emollient (G/P-emollient) cream on the lipid profiles of isolated ex vivo human SC and the SC of a reconstructed human epidermis (RHE) model was measured. Methods: The spatial organization of the cream and the isolated SC intercellular matrix were studied using X-ray diffraction. The inter-bilayer distances in the multi-lamellar lipid structures and lattice type were analyzed using small-angle X-ray scattering and wide-angle X-ray scattering (WAXS), respectively. Lipidomic analysis using shotgun lipidomics was performed on RHE models to quantify CER classes and chain lengths. This technology enables the analysis of thousands of lipids in a single biological sample. Results: The crystallized components of the cream are lipids, which were mainly packed in orthorhombic lattices, as well as hexagonal lattices and were similar to the SC structure. The cream penetrated the SC but did not alter the WAXS profile. It increased the amount of higher carbon number CERs (>42 carbons) and decreased lower carbon number CERs (<42 carbons). All chain length of CERs and acyl-CER classes (CER EOS, EOH, EOP, EOdS) were increased as the total CER classes. A decrease of the CER C34 for hydroxylated and non-hydroxylated CERs was also observed. The cream altered the S and P CER forms (increased the NP/NS and AP/AS ratios), indicating it could reduce the relative feedback mechanism observed in inflammatory pathologies, for example, atopic dermatitis. The cream increased CER NP, which is decreased in dry skin. Conclusion: G/P-emollient cream may be beneficial for skin pathologies by modifying SC lipids, balancing CER levels and ratios, and improving the barrier function. Importantly, the cream structure mimics that of the SC and penetrated the lower SC layers without compromising its lamellar structure.

Although the association between Too-Long Anterior Calcaneal Process (TLACP) and osteochondral lesion of the dome of the talus (OCL) has been hypothesized, no study has investigated the interrelations between TLACP, hind and mid-tarsal volumes and angles and the development of OCL. The main goals of this work are: (1) to measure the volume of the calcaneum, talus, navicular and cuboid in subjects with and without TLACP; (2) to evaluate the angular relationships between talus, calcaneum and navicular in subjects with and without TLACP; (3) to assess whether TLACP has an effect on the volume of OCL. This is a retrospective study of 69 CT scans of 54 consecutive children aged 11-15years who had undergone a CT scan due to symptomatology suggestive of TLACP. The 3D Slicer software allowed to calculate the volume of the talus, calcaneum, navicular, cuboid, TLACP and OCL (in cm3). The PACS system was used to perform the angular measurements (in degrees) between talus, calcaneum and navicular in the frontal, axial and sagittal plane. Amid the 69 CT scans, 49 were found to have pathologies related to TLACP (71%, TLACP Group) and 20/69 were normal (29%, Control Group). The mean hind and mid-tarsal bone volumes of the TLACP group were comparable to those of the control group. There were 40 (81.6%) OCLs detected exclusively in pathological feet (TLACP group); 32 lesions were medial (80%), and 8 lesions were lateral (20%). According to Ferkel and Sgaglione CT Staging System, there were 22 (55%) stage 1 lesions, 5 (12.5%) stage 2A, 3 (7.5%) stage 2B and 10 (25%) stage three lesions. Only the angle between the talus and calcaneum in the frontal plane was significantly lower in pathological feet with respect to the control group (p < 0.001). In pathological feet, the talus was supinated, and the calcaneus pronated. TLACP tend to stiffen the foot, modifying its biomechanics and leading to supination of the talus and pronation of the calcaneum. This induces an overpressure at the medial side of the talus where we observed a greater frequency of medial OCL with larger volume than lateral OCL. III.

Abstract Despite well-recognized difference in the atherosclerotic cardiovascular disease (ASCVD) risk between men and women, sex differences in risk factors and sex specific mechanisms in the pathophysiology of ASCVD remain poorly understood. Lipid metabolism plays a central role in the development of ASCVD. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in ASCVD and aid in precise risk assessment. Thus, we examined sex differences in plasma levels of 179 lipid species from 7,266 participants and performed sex-stratified genome-wide association studies (GWAS) to evaluate contribution of genetic factors in sex differences. We sought for replication using independent data from 2,045 participants. Significant sex differences in levels of 141 lipid species were observed (P&lt;7.0×10−4). Interestingly, 121 lipid species showed significant age-sex interactions with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids and glycerides were higher in 45-50-year-old men compared with women of same age, but the sex-differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex stratified GWAS which suggests that common genetic variants do not have a major role in sex differences in lipidome. In conclusion, our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism, highlighting need for sex- and age-specific prevention strategies.

ZusammenfassungIn diesem Kapitel knüpfe ich an die Vorüberlegungen der Kapitel zwei bis vier an und konkretisiere die Idee von bewegten Online-Seminaren anhand von neun bewegenden Methoden. Die Methoden dienen dem lernzeitwahrenden Bewegen in Online-Seminaren und können unterrichtsnah und fächerunabhängig in Unterricht, Hochschullehre und Erwachsenenbildung eingesetzt werden. Und noch etwas zeichnet sie aus: Die Methoden sind ganz einfach! Sie benötigen wenig Zeit, sie lassen sich leicht erklären. Sie lassen sich ganz unkompliziert in Ihre Online- und wahrscheinlich sogar in Ihre Präsenz-Seminare integrieren.

Method Associations between different biomarkers (proteomics, lipidomics, and metabolomics) coupled to either MHO or metabolically unhealthy obese (MUO) individuals were analyzed through principal component analysis (PCA). Subjects were identified from a subsample of 416 obese individuals, selected from the Malmö Diet and Cancer study—Cardiovascular arm (MDCS-CV, n = 3,443). They were further divided into MHO (n = 143) and MUO (n = 273) defined by a history of hospitalization, or not, at baseline inclusion, and nonobese subjects (NOC, n = 3,027). Two distinctive principle components (PL2, PP5) were discovered with a significant difference and thus further investigated through their main loadings. Results MHO individuals had a more metabolically favorable lipid and glucose profile than MUO subjects, that is, lower levels of traditional blood glucose and triglycerides, as well as a trend of lower metabolically unfavorable lipid biomarkers. PL2 (lipidomics, p=0.02) showed stronger associations of triacylglycerides with MUO, whereas phospholipids correlated with MHO. PP5 (proteomics, p=0.01) included interleukin-1 receptor antagonist (IL-1ra) and leptin with positive relations to MUO and galanin that correlated positively to MHO. The group differences in metabolite profiles were to a large extent explained by factors included in the metabolic syndrome. Conclusion Compared to MUO individuals, corresponding MHO individuals present with a more favorable lipid metabolic profile, accompanied by a downregulation of potentially harmful proteomic biomarkers. This unique and extensive biomarker profiling presents novel data on potentially differentiating traits between these two obese phenotypes.