Relationship between atopic dermatitis, depression and anxiety: a two-sample Mendelian randomization study.

BACKGROUND: Growing evidence suggests that atopic dermatitis (AD) is associated with an increased risk of depressive disorders and anxiety. However, existing studies were observational and may have uncovered correlations but could not easily disentangle noncausal or reverse-causal associations because these associations could be confounded and may not reflect true causal relationships. OBJECTIVES: To examine, in a two-sample Mendelian randomization study, the potential effect of AD on the risk of depressive disorders and anxiety. METHODS: Genetic instruments from the largest available genome-wide association study (GWAS) for AD (10 788 cases and 30 047 controls) were used to investigate the relationship to broad depression (170 756 cases and 329 443 controls), major depressive disorder (MDD; 30 603 cases and 143 916 controls) and anxiety (5580 cases and 11 730 controls). A set of complementary approaches were carried out to assess horizontal pleiotropy and related potential caveats occurring in MR studies. RESULTS: We observed no causal impact of AD on the risk of depressive disorders and anxiety, with close-to-zero effect estimates. The inverse weighted method revealed no associations of AD on broad depression [odds ratio (OR) 1·014; P = 0·431], probable MDD (OR 1·002; P = 0·568), International Classification of Diseases, Ninth/Tenth Revision-based MDD (OR 1·001; P = 0·466) or anxiety (OR 1·097; P = 0·180). CONCLUSIONS: This MR study does not support a causal effect of AD on depression and anxiety.

Host traits, lifestyle and environment are associated with human skin bacteria.

BACKGROUND: The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts with the broader knowledge about factors influencing gut microbiota. OBJECTIVES: We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations. METHODS: This is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1-V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). RESULTS: We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. CONCLUSIONS: We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.

Plasma membrane associated location of sulfonated meso-tetraphenylporphyrins of different hydrophilicity probed by total internal reflection fluorescence spectroscopy.

Sulfonated meso-tetraphenylporphyrins of different hydrophilicity were microspectrofluorimetrically examined in endothelial cells using total internal reflection (TIR) illumination or epi-illumination. Since the penetration depth of the evanescent field during TIR illumination is limited to a few hundred nanometers, photosensitizers were almost selectively examined in close vicinity to the plasma membrane. Pronounced fluorescence signals during TIR illumination were observed for the hydrophilic compounds meso-tetraphenylporphyrin tetrasulfonate (TPPS4) and meso-tetraphenylporphyrin trisulfonate (TPPS3), whereas the more lipophilic compounds meso-tetraphenylporphyrin disulfonate (TPPS2a) and meso-tetraphenylporphyrin monosulfonate (TPPS1) could only be detected under epi-illumination. Irradiation of TPPS1 and TPPS2a in the Soret band led to an increase in fluorescence intensity and formation of a photoproduct with an emission maximum around 610 nm, which was limited to intracellular compartments. In contrast, fluorescence spectra of TPPS3 and TPPS4 obtained by TIR and epi-illumination remained almost unchanged after irradiation in the Soret band. Extralysosomal location of TPPS3 and TPPS4 in close proximity to the plasma membrane was deduced from experiments with the lysosomal markers acridine orange (AO) or lysotracker yellow (LY), which were not detectable under TIR illumination. In conclusion, these results provide for the first time direct evidence for a plasma membrane-associated fraction of the hydrophilic compounds TPPS3 and TPPS4 in living cells.

Selective examination of plasma membrane-associated photosensitizers using total internal reflection fluorescence spectroscopy: correlation between photobleaching and photodynamic efficacy of protoporphyrin IX.

Fluorescence spectra, fluorescence decay kinetics, photobleaching kinetics and photodynamic efficacy of protoporphyrin IX (PP) were investigated in endothelial cells in vitro after different incubation times. Fluorescence spectra and photobleaching kinetics were determined during total internal reflection (TIR) illumination or epi-illumination. Because penetration depth of the excitation light during TIR illumination was limited to about 100 nm, plasma membrane-associated PP was almost selectively examined. Spectra obtained by TIR fluorescence spectroscopy (FS) showed a very low background, whereas spectra obtained by epi-illumination exhibited considerable background by autofluorescence and scattered light. For photobleaching kinetics during TIR illumination after 1 h or 24 h incubation, a biexponential fluorescence decrease was observed with a rapidly and a slowly bleaching portion. After 1 h incubation, the rapidly bleaching portion was the predominant fraction, whereas after 24 h incubation comparable relative amounts of the rapidly and slowly bleaching portion were determined. The rapidly and slowly bleaching portion were assigned to PP monomers and aggregated species in close vicinity to the plasma membrane. Fluorescence decay measurements after epi-illumination support the decrease of PP monomers within the whole cell with increasing incubation time. In contrast to TIR illumination, photobleaching of PP during epi-illumination was characterized by slow monoexponential fluorescence decrease after 1 h or 24 h incubation. Photodynamic efficacy of PP using epi-illumination was found to depend strongly on incubation time. Considerable cell inactivation was determined for short incubation times (1 h or 3 h), whereas photodynamic efficacy was diminished for longer incubation times. Reduced photodynamic efficacy after long incubation times was assigned to the lower amount of photodynamically active monomers determined close to the plasma membrane as well as within the whole cell. In conclusion, TIRFS measurements are suggested to be an appropriate tool for the examination of the plasma membrane-associated photosensitizer fraction in living cells.

Effects of lithium on electrical activity and potassium ion distribution in the vertebrate central nervous system.

Three different regions of the vertebrate central nervous system maintained in vitro (frog spinal cord, guinea pig olfactory cortex and hippocampus) have been used to investigate how Li+ influences membrane potential, membrane resistance, action potentials, synaptic potentials and the transmembrane K+-distribution of neurons and glial cells. In view of the therapeutic action of Li+ in manic-depressive disease, a special effort was made to determine the threshold concentration for the actions of Li+ on the parameters described above. It was observed that Li+ induced a membrane depolarization of both neurons and glial cells, a decrease of action potential amplitudes, a facilitation of monosynaptic excitatory postsynaptic potentials and a depression of polysynaptic reflexes. The membrane resistance of neurons was not altered. Li+ also induced an elevation of the free extracellular potassium concentration and a decrease of the free intracellular potassium concentration. Furthermore, in the presence of Li+ a slowing of the recovery of the membrane potential of neurons and glial cells, and of the extracellular potassium concentration after repetitive synaptic stimulation was observed. The threshold concentrations for the effects of Li+ were below 5 mmol/l in the frog spinal cord and below 2 mmol/l in the guinea pig olfactory cortex and hippocampus. The basic mechanism underlying the action of Li+ may be an interaction with the transport-function of the Na+/K+ pump.

Effect of adenosine versus adenine nucleotides on evoked potentials in a rat hippocampal slice preparation.

A marked depression of evoked CA1 potentials was observed with the nucleotide analogues a,b-methylene ADP (AOPCP) and adenylimido-diphosphate (AIP) and with 2'-adenosine monophosphate (2'-AMP). While the depression elicited by 5'-nucleotides was completely antagonized by the action of adenosine deaminase, AOPCP and 2'-AMP were only partially antagonized. The findings indicate that nucleotides on their own are capable of modulating synaptic transmission but that the physiologically more prevalent 5'-AMP is mediating its effect via adenosine. By producing this membrane permeable compound and allowing its re-uptake, the 5'-nucleotidase may determine the time course of purinergic action.

Glucose utilization during chromatolysis: a 14C deoxyglucose study.

After transection of the facial and hypoglossal nerves, rats were injected with 14C 2-deoxyglucose. Contact-autoradiographs of histological sections showed increased radioactivity in the motor nuclei of the operated side between 1 and 28 days post operation. This suggests an increase of glucose utilization and thus an enhanced energy supply to the facial and hypoglossal nuclei during the process of axonal reaction.