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Carbohydrates and lipids are not only energy sources and structural components of cells but fulfill very diverse and important roles in a multitude of cellular processes. The combination of a carbohydrate and a lipid linked via a glycosidic bond yields a glycolipid. Glycolipids occur in all kinds of organisms where they constitute major components of cell membranes, mediate cell-cell interactions and modulate immune responses. Their biological activities are highly dependent on their exact three-dimensional structures; however, the elucidation of glycolipid structures is inherently challenging due to the non-template-driven regio- and stereoselective synthesis of the carbohydrate and additional variations of the lipid moiety, such as length, saturation and hydroxylation. The modular biosynthesis of glycolipids generates many different and often isomeric combinations of glycans and lipids, which are not always distinguishable by standard analytical workflows based on liquid chromatography-mass spectrometry. The structural analysis of isomeric glycolipids thus requires orthogonal techniques yielding complementary information. In some cases, ion mobility spectrometry can be used to distinguish isomers based on their different cross sections in the gas phase. Another promising structure-sensitive technique is cryogenic gas phase infrared spectroscopy, which falls under the term action spectroscopy and yields highly resolved, reproducible IR spectra of isolated ions in the clean gas phase environment. In this work, sets of isomeric glycolipids were systematically investigated using ion mobility-mass spectrometry and cryogenic gas phase IR spectroscopy in helium nano- droplets. The obtained IR spectra of various isomeric glycosphingolipids bearing different monosaccharide headgroups are diagnostic for both the type of monosaccharide and the anomeric configuration because of very characteristic and reproducible absorption bands in the fingerprint region (1000–1150 cm-1). A more complex trisaccharide headgroup still yields a well-resolved IR fingerprint. The influence of the lipid part was examined by comparing IR spectra of glycolipids bearing the same headgroup but a different sphingoid base or a diacylglycerol. The exchange of phytosphingosine for sphingosine does not alter the fingerprint region significantly but influences the intensity of the amine bending vibration, whereas the introduction of a diacylglycerol changes the whole spectrum. The data show that cryogenic gas phase IR spectroscopy is a powerful technique to distinguish glycolipids bearing isomeric glycans up to a certain size, anomeric configurations and also subtle variations in the lipid moiety. Furthermore, the applicability of IR spectroscopy to distinguish double bond isomers was tested on synthetic derivatives of 1-deoxysphingosine. Depending on the position and configuration of the C C double bond, distinct N H bending modes of the protonated amine are observed. Gas phase IR spectroscopy could thus fill a gap in lipidomics, where lipid double bond isomers still pose a major challenge.

Depressive and anxiety disorders substantially contribute to the global burden of disease, particularly in poor countries. Higher prevalence rates for both disorders among women indicate sex hormones may be integrated in the pathophysiology of these disorders. The Kshetriya Gramin Financial Services study surveyed a random sample of 4,160 households across 876 villages in rural Tamil Nadu, India. An interviewer-administered questionnaire was conducted to quantify depressive (K6-D) and anxiety (K6-A) symptoms. Alongside, hair samples for sex hormone profiling were collected from a subsample of 2,105 women aged 18–85 years. Importantly, 5.9%, 14.8%, and 46.3% of samples contained non-detectable hormone levels for dehydroepiandrosterone, progesterone, and testosterone, respectively. Our primary analysis imputes values for the non-detectable sample and we check robustness of results when non-detectable values are dropped. In this cohort of women from rural India, higher depressive symptomatology is associated with lower levels of dehydroepiandrosterone and higher depressive and anxiety symptoms are associated with higher levels of testosterone. Progesterone shows no clear association with either depressive or anxiety symptoms. These results support a potential protective effect of higher endogenous dehydroepiandrosterone levels. An important caveat on the potential negative effect of hair testosterone levels on women’s mental health is that the testosterone analysis is sensitive to how non-detectable values are treated.

To gain a comprehensive understanding of the multidimensional complex systems structure of the stress response and related health outcomes, we utilized network analysis in a sample of 328 healthy participants in two steps. In a first step, we focused on associations between measures of basal hypothalamic-pituitary-adrenal axis functioning and subjective stress perceptions. In a second step, we linked these diverse stress-related measures to biomarkers and self-reports of health and sleep. Overall, measures clustered depending on their method of assessment, with high correlations between different saliva-based indices of diurnal cortisol regulation, between cortisol and cortisone levels in hair, between different biological health indicators (systemic inflammatory activity and body mass index), between state (experience sampling) and trait (questionnaire-based) self-reports of stress and wellbeing, and between different self-reports of sleep. Bridges between clusters suggested that if individuals perceive stress throughout their daily lives this is reflected in their total salivary cortisol output possibly contributing to long-term cortisol accumulation in hair. Likewise, earlier awakening time may contribute to cortisol accumulation in hair via an influence on awakening cortisol processes. Our results show that while meaningful connections between measures exist, stress is a highly complex construct composed of numerous aspects. We argue that network analysis is an integrative statistical approach to address the multidimensionality of the stress response and its effects on the brain and body. This may help uncover pathways to stress-related disease and serve to identify starting points for prevention and therapeutic intervention. © 2018 Elsevier Inc.