Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. ...High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associated with BMI in both sexes (with a larger effect size in men), whilst acylcarnitine species showed opposing associations based on sex (positive association in women and negative association in men). Finally, by utilising specific lipid ratios as a proxy for enzymatic activity, we identified stearoyl CoA desaturase (SCD-1), fatty acid desaturase 3 (FADS3), and plasmanylethanolamine Δ1-desaturase activities, as well as the sphingolipid metabolic pathway, as constituent perturbations of cardiometabolic phenotypes. Our analyses elucidate the effect of age and sex on lipid metabolism by offering a comprehensive view of the lipidomic profiles associated with common cardiometabolic risk factors. These findings have implications for age- and sex-dependent lipid metabolism in health and disease and suggest the need for sex stratification during lipid biomarker discovery, establishing biological reference intervals for assessment of disease risk.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer's disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating ...detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM
gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation.
Abstract
We introduce new methods to numerically construct for the first time stationary axisymmetric black hole solutions in Einstein-aether theory and study their properties. The key technical ...challenge is to impose regularity at the spin-2, 1, and 0 wave mode horizons. Interestingly we find the metric horizon, and various wave mode horizons, are not Killing horizons, having null generators to which no linear combination of Killing vectors is tangent, and which spiral from pole to equator or vice versa. Existing phenomenological constraints result in two regions of coupling parameters where the theory is viable and some couplings are large; region I with a large twist coupling and region II with also a (somewhat) large expansion coupling. Currently these constraints do not include tests from strong field dynamics, such as observations of black holes and their mergers. Given the large aether coupling(s) one might expect such dynamics to deviate significantly from general relativity (GR), and hence to further constrain the theory. Here we argue this is not the case, since for these parameter regions solutions exist where the aether is ‘painted’ onto a metric background that is very close to that of GR. This painting for region I is approximately independent of the large twist coupling, and for region II is also approximately independent of the large expansion coupling and normal to a maximal foliation of the spacetime. We support this picture analytically for weak fields, and numerically for rotating black hole solutions, which closely approximate the Kerr metric.
MicroScope is an integrated platform dedicated to both the methodical updating of microbial genome annotation and to comparative analysis. The resource provides data from completed and ongoing genome ...projects (automatic and expert annotations), together with data sources from post-genomic experiments (i.e. transcriptomics, mutant collections) allowing users to perfect and improve the understanding of gene functions. MicroScope (http://www.genoscope.cns.fr/agc/microscope) combines tools and graphical interfaces to analyse genomes and to perform the manual curation of gene annotations in a comparative context. Since its first publication in January 2006, the system (previously named MaGe for Magnifying Genomes) has been continuously extended both in terms of data content and analysis tools. The last update of MicroScope was published in 2009 in the Database journal. Today, the resource contains data for >1600 microbial genomes, of which ∼300 are manually curated and maintained by biologists (1200 personal accounts today). Expert annotations are continuously gathered in the MicroScope database (∼50 000 a year), contributing to the improvement of the quality of microbial genomes annotations. Improved data browsing and searching tools have been added, original tools useful in the context of expert annotation have been developed and integrated and the website has been significantly redesigned to be more user-friendly. Furthermore, in the context of the European project Microme (Framework Program 7 Collaborative Project), MicroScope is becoming a resource providing for the curation and analysis of both genomic and metabolic data. An increasing number of projects are related to the study of environmental bacterial (meta)genomes that are able to metabolize a large variety of chemical compounds that may be of high industrial interest.
The fast charging capability of lithium-ion batteries is mainly constricted by mass transport limitations within the electrolyte that fills the porous network of the electrodes. The onset of a ...parasitic side reaction referred to as lithium plating strongly depends on the micro-structure of the batteries’ anode. In this study, a methodology is introduced that allows to investigate the influence of the slurry preparation on electrode properties and the resulting fast charging performance of graphite anodes. Therefore, an in-situ lithium plating detection technique based on the differential charging voltage is used to connect electrode properties with the fast charging capability of the anodes in lithium-ion cells. Following this approach, changes in the particle size distribution due to a high intensity mixing process using pilot-plant scaled planetary mixers are linked to a modification of the pore size distribution and the electrode tortuosity. Eventually, a deteriorated fast charging performance is connected to the increased tortuosity caused by high intensity mixing.
•Method to understand process-structure-property relationship for slurry mixing.•Relationship between anode porosity and onset of lithium plating.•High intensity slurry mixing results in abrasion of graphite particles.•Altered particle size and morphology result in diffusion-impeding pore structure.•Onset of lithium plating correlates with impedance-derived anode tortuosity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This article applies constructs from the Self-Medication Hypothesis and Social Cognitive Theory to explain the development of substance use and psychological distress after a disaster. A conceptual ...model is proposed, which employs a sequential mediation model, identifying perceived coping self-efficacy, psychological distress, and self-medication as pathways to substance use after a disaster. Disaster exposure decreases perceived coping self-efficacy, which, in turn, increases psychological distress and subsequently increases perceptions of self-medication in vulnerable individuals. These mechanisms lead to an increase in postdisaster substance use. Last, recommendations are offered to encourage disaster researchers to test more complex models in studies on postdisaster psychological distress and substance use.
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DOBA, IJS, NUK, SIK, UILJ, UKNU, UL, UM, UPUK
Over the last few years Pohl (partly jointly with coauthors) has developed dual ‘slow/fast’ transfer operator approaches to automorphic functions, resonances, and Selberg zeta functions for a certain ...class of hyperbolic surfaces
$\unicodeSTIX{x1D6E4}\backslash \mathbb{H}$
with cusps and all finite-dimensional unitary representations
$\unicodeSTIX{x1D712}$
of
$\unicodeSTIX{x1D6E4}$
. The eigenfunctions with eigenvalue 1 of the fast transfer operators determine the zeros of the Selberg zeta function for
$(\unicodeSTIX{x1D6E4},\unicodeSTIX{x1D712})$
. Further, if
$\unicodeSTIX{x1D6E4}$
is cofinite and
$\unicodeSTIX{x1D712}$
is the trivial one-dimensional representation then highly regular eigenfunctions with eigenvalue 1 of the slow transfer operators characterize Maass cusp forms for
$\unicodeSTIX{x1D6E4}$
. Conjecturally, this characterization extends to more general automorphic functions as well as to residues at resonances. In this article we study, without relying on Selberg theory, the relation between the eigenspaces of these two types of transfer operators for any Hecke triangle surface
$\unicodeSTIX{x1D6E4}\backslash \mathbb{H}$
of finite or infinite area and any finite-dimensional unitary representation
$\unicodeSTIX{x1D712}$
of the Hecke triangle group
$\unicodeSTIX{x1D6E4}$
. In particular, we provide explicit isomorphisms between relevant subspaces. This solves a conjecture by Möller and Pohl, characterizes some of the zeros of the Selberg zeta functions independently of the Selberg trace formula, and supports the previously mentioned conjectures.
Emerging research identified physical inactivity and weight-related comorbidities as significant risk factors for contracting SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), reinforcing ...the importance of maintaining regular exercise during the pandemic. Previous scholarship in this area examined the impact of coronavirus disease 2019 (COVID-19) across various populations. Currently, there is limited research examining how these populations engage in and navigate challenges relating to exercise during shelter-in-place mandates and no studies examining the role of social support in promoting exercise during the pandemic. In this study, we examine perceptions of social support during the COVID-19 pandemic among members who belong to a fitness community based in Oakland, California. In-depth interviews (n = 31) were used to understand how the pandemic has affected participants’ perceptions of current exercise habits and how understandings of social support facilitate engagement in physical activity. Reported narratives encompassed two primary themes: (1) Facilitators of Social Support and (2) Challenges and Barriers to Social Support. Our findings highlight the importance of social support for reinforcing perceptions of exercise adherence amid challenges experienced by members of a fitness community to remain physically active during the COVID-19 pandemic.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The dendritic cell signals required for the in vivo priming of IL-4-producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN of mice exposed to two different Th2 ...stimuli: the helminth parasite Nippostrongylus brasiliensis (Nb) and the contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb and DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these transcriptional changes were highly distinct in the two models, with only a small number of genes being similarly regulated in both conditions. Pathway analysis of expressed genes identified no shared pathways between Nb and DBP-FITC, but revealed a type-I IFN (IFN-I) signature unique to DCs from Nb-primed mice. Blocking the IFN-I receptor at the time of Nb treatment had little effect on DC migration and antigen transport to the LN, but inhibited the up-regulation of IFN-I-induced markers on DCs and effectively blunted Th2 development. In contrast, the response to DBP-FITC was not affected by IFN-I receptor blockade, a finding consistent with the known dependence of this response on the innate cytokine TSLP. Thus, the priming of Th2 responses is associated with distinct transcriptional signatures in DCs in vivo, reflecting the diverse environments in which Th2 immune responses are initiated.
There is mounting evidence that in utero and early life exposures may predispose an individual to metabolic disorders in later life; and dysregulation of lipid metabolism is critical in such ...outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. We studied the effect of antenatal factors such as gestational age, birth weight, and mode of birth on lipid metabolism at birth; changes in the circulating lipidome in the first 4 years of life and the effect of breastfeeding in the first year of life. From this study, we aim to generate a framework for deeper understanding into factors effecting lipid metabolism in early life, to provide early interventions for those at risk of developing metabolic disorders including cardiovascular diseases.
We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population-based pre-birth cohort and measured 776 distinct lipid features across 39 lipid classes using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We measured lipids in 1032 maternal serum samples at 28 weeks' gestation, 893 cord serum samples at birth, 793, 735, and 511 plasma samples at 6, 12 months, and 4 years, respectively. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. We performed regression analyses to investigate the associations of cord serum lipid species with antenatal factors: gestational age, birth weight, mode of birth and duration of labour.
The lipidome differed between mother and newborn and changed markedly with increasing child's age. Alkenylphosphatidylethanolamine species containing LC-PUFAs increased with child's age, whereas the corresponding lysophospholipids and triglycerides decreased. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. Breastfeeding had a significant impact on the plasma lipidome in the first year of life, with up to 17-fold increases in a few species of alkyldiaclylglycerols at 6 months of age.
This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood.
This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
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