Circulating metabolites modulated by diet are associated with depression

Metabolome reflects the interplay of genome and exposome at molecular level and thus can provide deep insights into the pathogenesis of a complex disease like major depression. To identify metabolites associated with depression we performed a metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, and circulating metabolites using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based Metabolon platform. We tested 806 metabolites covering a wide range of biochemical processes including those involved in lipid, amino-acid, energy, carbohydrate, xenobiotic and vitamin metabolism for their association with depression. In a conservative model adjusting for life style factors and cardiovascular and antidepressant medication use we identified 8 metabolites, including 6 novel, significantly associated with depression. In individuals with depression, increased levels of retinol (vitamin A), 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1) (lecithin) and mannitol/sorbitol and lower levels of hippurate, 4-hydroxycoumarin, 2-aminooctanoate (alpha-aminocaprylic acid), 10-undecenoate (11:1n1) (undecylenic acid), 1-linoleoyl-GPA (18:2) (lysophosphatidic acid; LPA 18:2) are observed. These metabolites are either directly food derived or are products of host and gut microbial metabolism of food-derived products. Our Mendelian randomization analysis suggests that low hippurate levels may be in the causal pathway leading towards depression. Our findings highlight putative actionable targets for depression prevention that are easily modifiable through diet interventions.</p

A scanning single-electron transistor array microscope probes the Hall potential profile in the fractional quantum Hall regime

INTRO: In 1980 Klaus von Klitzing (Nobel prize in 1985) observed during low-temperature Hall measurements on two-dimensional electron systems hosted by MOSFETs, fixed values of the Hall resistances R_xy described with h/(ie^2) (i is integer) - nowadays denoted as integer quantum Hall effect (QHE). Since 1990 the QHE is used as a resistance standard and it played a key role in the redefinition of the Système Internationale d'unités (SI unit system), where from May 2019 the SI units are defined by fixing the values of fundamental physical constants as h, e, c and k_B. In 1982 Störmer, Tsui and Laughlin (Nobel prize in 1998) observed and discussed the fractional quantum Hall effect (FQHE) where further resistance plateaus are observable with R_xy=h/(ve^2) where v are special fractional numbers. The FQHE is currently understood on base of electron-electron interaction leading to quasi-particles with fractional effective charge. The main goal of this thesis was to use an one-dimensional single-electron transistor (SET) array as sensitive electrometer to locally probe Hall potential profiles in the fractional quantum Hall regime to determine where an externally biased current is distributed inside a two-dimensional electron system (2DES) hosted by an (Al,Ga)As heterostructure. MICROSCOPIC PICTURE: This thesis opens with an explanation of the microscopic picture of the integer quantum Hall effect where strong magnetic flux densities lead to the formation of Landau levels that are separated by an energy gap. This gap is responsible for the formation of electrically incompressible regions - with a well defined integer filling factor - within an otherwise compressible 2DES. A quantum Hall plateau shows two regimes: (1) the edge-dominated QH regime in the low magnetic field side and (2) the bulk-dominated QH regime in the high magnetic side of the plateau. SCANNING SET ARRAY MICROSCOPE: For experiments a scanning single-electron transistor (SET) array microscope with eight independent SETs on tips is used. The SET island sizes are about 155nm by 220nm, separated by 4µm. Single-electron charging energies up to 175µeV had been reached for these SETs. Measurements were performed at temperatures below 40mK in a 3He/4He dilution refrigerator with a 18T superconducting magnet, located in a highly vibrational reduced environment. MEASUREMENT PRINCIPLE: Electrostatic potential changes of the 2DES which result solely from an externally biased current are accessible via a two-step measurement technique probing calibrated Hall potential profiles. In this thesis a new method to extract and present local current density distributions from such Hall potential profiles is introduced. EXPERIMENTAL RESULTS: After systematic measurements of Hall potential profiles in the integer quantum Hall regime around filling factors v={3,2,1} the fractional quantum Hall regime with filling factors v=2/3 and v=3/5 is investigated for the first time with a scanning SET array microscope. Experimental results show a similar behavior for fractional and integer filling factors: (1) Hall potential profiles probed across the sample width evolve for varying magnetic flux densities in the same way, (2) the longitudinal resistance R_xx shows the same electrical breakdown behavior and (3) area scans in the fractional quantum Hall regime at fixed magnetic fields are spatially homogeneous. These similarities are seen for the first time and they contradict the widely used picture of a current transport along the edge. A final discussion at the end clarified, that the integer QH regime and the fractional QH regime have generally one thing in common: There is an evolution of the compressible/incompressible landscape within the 2DES which determines the current distribution in the 2DES. NEW SENSOR DEVELOPMENT: Additionally, a further milestone to the functionality of our scanning single-electron array microscope is developed: A free-standing Hall sensor tip which (i) allows another access to the current distribution inside the 2DES and (ii) makes also diamagnetic currents, which are already present in equilibrium, accessible. A calculation shows that this sensor can detect electrostatics and magnetic fields separately when a feedback loop is used

Inhibition of predator attraction to kairomones by non-host plant volatiles for herbivores: a bypass-trophic signal

Background Insect predators and parasitoids exploit attractive chemical signals from lower trophic levels as kairomones to locate their herbivore prey and hosts. We hypothesized that specific chemical cues from prey non-hosts and non-habitats, which are not part of the trophic chain, are also recognized by predators and would inhibit attraction to the host/prey kairomone signals. To test our hypothesis, we studied the olfactory physiology and behavior of a predaceous beetle, Thanasimus formicarius (L.) (Coleoptera: Cleridae), in relation to specific angiosperm plant volatiles, which are non-host volatiles (NHV) for its conifer-feeding bark beetle prey. Methodology/Principal Findings Olfactory detection in the clerid was confirmed by gas chromatography coupled to electroantennographic detection (GC-EAD) for a subset of NHV components. Among NHV, we identified two strongly antennally active molecules, 3-octanol and 1-octen-3-ol. We tested the potential inhibition of the combination of these two NHV on the walking and flight responses of the clerid to known kairomonal attractants such as synthetic mixtures of bark beetle (Ips spp.) aggregation pheromone components (cis-verbenol, ipsdienol, and E-myrcenol) combined with conifer (Picea and Pinus spp.) monoterpenes (α-pinene, terpinolene, and Δ3-carene). There was a strong inhibitory effect, both in the laboratory (effect size d = −3.2, walking bioassay) and in the field (d = −1.0, flight trapping). This is the first report of combining antennal detection (GC-EAD) and behavioral responses to identify semiochemical molecules that bypass the trophic system, signaling habitat information rather than food related information. Conclusions/Significance Our results, along with recent reports on hymenopteran parasitoids and coleopteran predators, suggest that some NHV chemicals for herbivores are part of specific behavioral signals for the higher trophic level and not part of a background noise. Such bypass-trophic signals could be of general importance for third trophic level players in avoiding unsuitable habitats with non-host plants of their prey