Cortical surface area alterations shaped by genetic load for neuroticism.

Neuroticism has been shown to act as an important risk factor for major depressive disorder (MDD). Genetic and neuroimaging research has independently revealed biological correlates of neurotic personality including cortical alterations in brain regions of high relevance for affective disorders. Here we investigated the influence of a polygenic score for neuroticism (PGS) on cortical brain structure in a joint discovery sample of n = 746 healthy controls (HC) and n = 268 MDD patients. Findings were validated in an independent replication sample (n = 341 HC and n = 263 MDD). Subgroup analyses stratified for case-control status and analyses of associations between neurotic phenotype and cortical measures were carried out. PGS for neuroticism was significantly associated with a decreased cortical surface area of the inferior parietal cortex, the precuneus, the rostral cingulate cortex and the inferior frontal gyrus in the discovery sample. Similar associations between PGS and surface area of the inferior parietal cortex and the precuneus were demonstrated in the replication sample. Subgroup analyses revealed negative associations in the latter regions between PGS and surface area in both HC and MDD subjects. Neurotic phenotype was negatively correlated with surface area in similar cortical regions including the inferior parietal cortex and the precuneus. No significant associations between PGS and cortical thickness were detected. The morphometric overlap of associations between both PGS and neurotic phenotype in similar cortical regions closely related to internally focused cognition points to the potential relevance of genetically shaped cortical alterations in the development of neuroticism.

Influence of electroconvulsive therapy on white matter structure in a diffusion tensor imaging study.

BACKGROUND: Electroconvulsive therapy (ECT) is a fast-acting intervention for major depressive disorder. Previous studies indicated neurotrophic effects following ECT that might contribute to changes in white matter brain structure. We investigated the influence of ECT in a non-randomized prospective study focusing on white matter changes over time. METHODS: Twenty-nine severely depressed patients receiving ECT in addition to inpatient treatment, 69 severely depressed patients with inpatient treatment (NON-ECT) and 52 healthy controls (HC) took part in a non-randomized prospective study. Participants were scanned twice, approximately 6 weeks apart, using diffusion tensor imaging, applying tract-based spatial statistics. Additional correlational analyses were conducted in the ECT subsample to investigate the effects of seizure duration and therapeutic response. RESULTS: Mean diffusivity (MD) increased after ECT in the right hemisphere, which was an ECT-group-specific effect. Seizure duration was associated with decreased fractional anisotropy (FA) following ECT. Longitudinal changes in ECT were not associated with therapy response. However, within the ECT group only, baseline FA was positively and MD negatively associated with post-ECT symptomatology. CONCLUSION: Our data suggest that ECT changes white matter integrity, possibly reflecting increased permeability of the blood-brain barrier, resulting in disturbed communication of fibers. Further, baseline diffusion metrics were associated with therapy response. Coherent fiber structure could be a prerequisite for a generalized seizure and inhibitory brain signaling necessary to successfully inhibit increased seizure activity.

L-Erythrulose production with a multideletion strain of Gluconobacter oxydans.

Many ketoses or organic acids can be produced by membrane-associated oxidation with Gluconobacter oxydans. In this study, the oxidation of meso-erythritol to L-erythrulose was investigated with the strain G. oxydans 621HΔupp BP.8, a multideletion strain lacking the genes for eight membrane-bound dehydrogenases. First batch biotransformations with growing cells showed re-consumption of L-erythrulose by G. oxydans 621HΔupp BP.8 in contrast to resting cells. The batch biotransformation with 2.8 g L-1 resting cells of G. oxydans 621HΔupp BP.8 in a DO-controlled stirred-tank bioreactor resulted in 242 g L-1 L-erythrulose with a product yield of 99% (w/w) and a space-time yield of 10 g L-1 h-1. Reaction engineering studies showed substrate excess inhibition as well as product inhibition of G. oxydans 621HΔupp BP.8 in batch biotransformations. In order to overcome substrate inhibition, a continuous membrane bioreactor with full cell retention was applied for meso-erythritol oxidation with resting cells of G. oxydans 621HΔupp BP.8. At a mean hydraulic residence time of 2 h, a space-time yield of 27 g L-1 h-1 L-erythrulose was achieved without changing the product yield of 99% (w/w) resulting in a cell-specific product yield of up to 4.4 gP gX-1 in the steady state. The product concentration (54 g L-1 L-erythrulose) was reduced in the continuous biotransformation process compared with the batch process to avoid product inhibition.

Asymmetric Whole-Cell Bio-Reductions of (R)-Carvone Using Optimized Ene Reductases.

(2R,5R)-dihydrocarvone is an industrially applied building block that can be synthesized by site-selective and stereo-selective C=C bond bio-reduction of (R)-carvone. Escherichia coli (E. coli) cells overexpressing an ene reductase from Nostoc sp. PCC7120 (NostocER1) in combination with a cosubstrate regeneration system proved to be very effective biocatalysts for this reaction. However, the industrial applicability of biocatalysts is strongly linked to the catalysts' activity. Since the cell-internal NADH concentrations are around 20-fold higher than the NADPH concentrations, we produced E. coli cells where the NADPH-preferring NostocER1 was exchanged with three different NADH-accepting NostocER1 mutants. These E. coli whole-cell biocatalysts were used in batch operated stirred-tank reactors on a 0.7 l-scale for the reduction of 300 mM (R)-carvone. 287 mM (2R,5R)-dihydrocarvone were formed within 5 h with a diasteromeric excess of 95.4% and a yield of 95.6%. Thus, the whole-cell biocatalysts were strongly improved by using NADH-accepting enzymes, resulting in an up to 2.1-fold increased initial product formation rate leading to a 1.8-fold increased space-time yield when compared to literature.

Effects of cumulative illness severity on hippocampal gray matter volume in major depression: a voxel-based morphometry study.

BACKGROUND: Patients with major depression show reduced hippocampal volume compared to healthy controls. However, the contribution of patients' cumulative illness severity to hippocampal volume has rarely been investigated. It was the aim of our study to find a composite score of cumulative illness severity that is associated with hippocampal volume in depression. METHODS: We estimated hippocampal gray matter volume using 3-tesla brain magnetic resonance imaging in 213 inpatients with acute major depression according to DSM-IV criteria (employing the SCID interview) and 213 healthy controls. Patients' cumulative illness severity was ascertained by six clinical variables via structured clinical interviews. A principal component analysis was conducted to identify components reflecting cumulative illness severity. Regression analyses and a voxel-based morphometry approach were used to investigate the influence of patients' individual component scores on hippocampal volume. RESULTS: Principal component analysis yielded two main components of cumulative illness severity: Hospitalization and Duration of Illness. While the component Hospitalization incorporated information from the intensity of inpatient treatment, the component Duration of Illness was based on the duration and frequency of illness episodes. We could demonstrate a significant inverse association of patients' Hospitalization component scores with bilateral hippocampal gray matter volume. This relationship was not found for Duration of Illness component scores. CONCLUSIONS: Variables associated with patients' history of psychiatric hospitalization seem to be accurate predictors of hippocampal volume in major depression and reliable estimators of patients' cumulative illness severity. Future studies should pay attention to these measures when investigating hippocampal volume changes in major depression.

Prefrontal brain responsiveness to negative stimuli distinguishes familial risk for major depression from acute disorder.

BACKGROUND: Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psychiatric research. In individuals with acute MDD, dysfunctional connectivity patterns of prefrontal areas have been shown repeatedly. However, it has been unclear in which neuronal networks functional alterations in individuals at familial risk for MDD might be present and to what extent they resemble findings previously reported in those with acute MDD. METHODS: We investigated differences in blood oxygen level-dependent (BOLD) response of the medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to aversive stimuli between acute MDD and familial risk for the disorder in healthy first-degree relatives of acutely depressed patients with MDD (HC-FH+), healthy age- and sex-matched controls without any family history of depression (HC-FH-), and acutely depressed patients with MDD with (MDD-FH+) and without a family history of depression (MDD-FH-) during a frequently used emotional face-matching paradigm. Analyses of task-specific network connectivity were conducted in terms of psychophysiological interactions (PPI). RESULTS: The present analysis included a total of 100 participants: 25 HC-FH+, 25 HC-FH-, 25 MDD-FH+ and 25 MDD-FH-. Patients with MDD exhibited significantly increased activation in the medial OFC to negative stimuli irrespective of familial risk status, whereas healthy participants at familial risk and patients with MDD alike showed significant hypoactivation in the DLPFC compared with healthy participants without familial risk. The PPI analyses revealed significantly enhanced task-specific coupling between the medial OFC and differing cortical areas in individuals with acute MDD and those with familial risk for the disorder. LIMITATIONS: The main limitation of our study is its cross-sectional design. CONCLUSION: Whereas hypoactivation during negative emotion processing in the DLPFC appears as a common feature in both healthy high-risk individuals and acutely depressed patients, activation patterns of the medial OFC and its underlying connectivity seem to distinguish familial risk from acute disorder.

Octave spanning wedge dispersive mirrors with low dispersion oscillations.

A novel concept for octave spanning dispersive mirrors with low spectral dispersion oscillations is presented. The key element of the so-called wedge dispersive mirror is a slightly wedged layer which is coated on a specially optimized dispersive multilayer stack by a common sputter coating process. The group delay dispersion (GDD) of a pulse reflected on a wedge dispersive mirror is nearly free of oscillations. Fabricated mirrors with negative GDD demonstrate the compression of a pulse down to 3.8 fs as good as double angled mirrors optimized for the same bandwidth.

Visualization of bond rearrangements in acetylene using near single-cycle laser pulses.

The migration of hydrogen atoms resulting in the isomerization of hydrocarbons is an important process which can occur on ultrafast timescales. Here, we visualize the light-induced hydrogen migration of acetylene to vinylidene in an ionic state using two synchronized 4 fs intense laser pulses. The first pulse induces hydrogen migration, and the second is used for monitoring transient structural changes via Coulomb explosion imaging. Varying the time delay between the pulses reveals the migration dynamics with a time constant of 54 ± 4 fs as observed in the H+ + H+ + CC+ channel. Due to the high temporal resolution, vibrational wave-packet motions along the CC- and CH-bonds are observed. Even though a maximum in isomerization yield for kinetic energy releases above 16 eV is measured, we find no indication for a backwards isomerization - in contrast to previous measurements. Here, we propose an alternative explanation for the maximum in isomerization yield, namely the surpassing of the transition state to the vinylidene configuration within the excited dication state.

Exploring the nature of cellulose microfibrils.

Ultrathin cellulose microfibril fractions were extracted from spruce wood powder using combined delignification, TEMPO-catalyzed oxidation, and sonication processes. Small-angle X-ray scattering of these microfibril fractions in a "dilute" aqueous suspension (concentration 0.077 wt %) revealed that their shape was in the form of nanostrip with 4 nm width and only about 0.5 nm thicknesses. These dimensions were further confirmed by TEM and AFM measurements. The 0.5 nm thickness implied that the nanostrip could contain only a single layer of cellulose chains. At a higher concentration (0.15 wt %), SAXS analysis indicated that these nanostrips aggregated into a layered structure. The X-ray diffraction of samples collected at different preparation stages suggested that microfibrils were delaminated along the (11̅0) planes from the Iß cellulose crystals. The degree of oxidation and solid-state (13)C NMR characterizations indicated that, in addition to the surface molecules, some inner molecules of microfibrils were also oxidized, facilitating the delamination into cellulose nanostrips.

AI-based automated detection and stability analysis of traumatic vertebral body fractures on computed tomography.

PURPOSE: We developed and tested a neural network for automated detection and stability analysis of vertebral body fractures on computed tomography (CT). MATERIALS AND METHODS: 257 patients who underwent CT were included in this Institutional Review Board (IRB) approved study. 463 fractured and 1883 non-fractured vertebral bodies were included, with 190 fractures unstable. Two readers identified vertebral body fractures and assessed their stability. A combination of a Hierarchical Convolutional Neural Network (hNet) and a fracture Classification Network (fNet) was used to build a neural network for the automated detection and stability analysis of vertebral body fractures on CT. Two final test settings were chosen: one with vertebral body levels C1/2 included and one where they were excluded. RESULTS: The mean age of the patients was 68 ± 14 years. 140 patients were female. The network showed a slightly higher diagnostic performance when excluding C1/2. Accordingly, the network was able to distinguish fractured and non-fractured vertebral bodies with a sensitivity of 75.8 % and a specificity of 80.3 %. Additionally, the network determined the stability of the vertebral bodies with a sensitivity of 88.4 % and a specificity of 80.3 %. The AUC was 87 % and 91 % for fracture detection and stability analysis, respectively. The sensitivity of our network in indicating the presence of at least one fracture / one unstable fracture within the whole spine achieved values of 78.7 % and 97.2 %, respectively, when excluding C1/2. CONCLUSION: The developed neural network can automatically detect vertebral body fractures and evaluate their stability concurrently with a high diagnostic performance.

Nanofibrous microfiltration membrane based on cellulose nanowhiskers.

A multilayered nanofibrous microfiltration (MF) membrane system with high flux, low pressure drop, and high retention capability against both bacteria and bacteriophages (a virus model) was developed by impregnating ultrafine cellulose nanowhiskers (diameter about 5 nm) into an electrospun polyacrylonitrile (PAN) nanofibrous scaffold (fiber diameter about 150 nm) supported by a poly(ethylene terephthalate) (PET) nonwoven substrate (fiber diameter about 20 µm). The cellulose nanowhiskers were anchored on the PAN nanofiber surface, forming a cross-linked nanostructured mesh with very high surface-to-volume ratio and a negatively charged surface. The mean pore size and pore size distribution of this MF system could be adjusted by the loading of cellulose nanowhiskers, where the resulting membrane not only possessed good mechanical properties but also high surface charge density confirmed by the conductivity titration and zeta potential measurements. The results indicated that a test cellulose nanowhisker-based MF membrane exhibited 16 times higher adsorption capacity against a positively charged dye over a commercial nitrocellulose-based MF membrane. This experimental membrane also showed full retention capability against bacteria, for example, E. coli and B. diminuta (log reduction value (LRV) larger than 6) and decent retention against bacteriophage MS2 (LRV larger than 2).

Ultrafine polysaccharide nanofibrous membranes for water purification.

Ultrafine polysaccharide nanofibers (i.e., cellulose and chitin) with 5-10 nm diameters were employed as barrier layers in a new class of thin-film nanofibrous composite (TFNC) membranes for water purification. In addition to concentration, the viscosity of the polysaccharide nanofiber coating suspension was also found to be affected by the pH value and ionic strength. When compared with two commercial UF membranes (PAN10 and PAN400), 10-fold higher permeation flux with above 99.5% rejection ratio were achieved by using ultrafine cellulose nanofibers-based TFNC membranes for ultrafiltration of oil/water emulsions. The very high surface-to-volume ratio and negatively charged surface of cellulose nanofibers, which lead to a high virus adsorption capacity as verified by MS2 bacteriophage testing, offer further opportunities in drinking water applications. The low cost of raw cellulose/chitin materials, the environmentally friendly fabrication process, and the impressive high-flux performance indicate that such ultrafine polysaccharide nanofibers-based TFNC membranes can surpass conventional membrane systems in many different water applications.

Non-Born-Oppenheimer Molecular Dynamics Observed by Coherent Nuclear Wave Packets.

The reaction dynamics of a photochemical reaction is typically described by reaction coordinates based on the Born-Oppenheimer (BO) approximation. A strong interaction between electrons and nuclei, conventionally occurring at conical intersections, however, breaks the BO approximation and has major consequences for the efficiency of a photochemical reaction. Despite its importance, related studies into the non-BO dynamics are scarce. Here, we investigate the non-BO dynamics of excited-state intramolecular proton transfer (ESIPT) occurring in 10-hydroxybenzo[h]quinoline (HBQ). Two coherent vibrational modes at 237 and 794 cm-1 representing molecular dynamics on a diabatic surface in HBQ are identified by a wave packet analysis based on a transient absorption measurement with a time resolution of 11 fs and with a density functional theory-based model calculation. It is also revealed that the strong Coulomb field effect in HBQ leads to the completion of ESIPT within about two cycles of the OH stretching mode. The work paves the way for time-domain studies of molecular dynamics beyond the BO approximation in other photochemical reactions.

The genetic architecture of the human cerebral cortex.

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Block copolymers with a twist.

Chiral block copolymers (BCPs*) comprising chiral entities were designed to fabricate helical architectures (i.e., twisted morphologies) from self-assembly. A new helical phase (H*) with P622 symmetry was discovered in the self-assembly of poly(styrene)-b-poly(l-lactide) (PS-PLLA) BCPs*. Hexagonally packed, interdigitated PLLA helical microdomains in a PS matrix were directly visualized by electron tomography. The phase diagram of the PS-PLLA BCPs* was also established. Phase transitions from the H* phase to the stable cylinder and gyroid phases were found after long-time annealing, suggesting that the H* is a long-lived metastable phase. In contrast to racemic poly(styrene)-b-poly(d,l-lactide) BCPs, chiral interaction significantly enhances the incompatibility between achiral PS and chiral PLLA blocks in the PS-PLLA BCPs* and can be estimated through the determination of the interaction parameter.

Use of a robotic RNA purification protocol based on the NucliSens easyMAG for real-time RT-PCR detection of hepatitis A virus in bottled water.

Hepatitis A virus (HAV) infection is the leading cause of acute viral hepatitis throughout the world. An important part of viral control is rapid detection of HAV in drinking water contaminated with feces. One critical step in HAV detection methods is sample preparation. The objective of this study was to test the efficacy of different approaches to extracting RNA from HAV-inoculated bottled water. The optimal method is based on viral concentration by filtration on membrane filters and elution of adsorbed viruses from filters before RNA extraction and RT-PCR amplification. In this approach, the commercially available NucliSens easyMAG bio-robot (Biomérieux) performs viral RNA purification with silica magnetic beads, which mediate purification of nucleic acids by binding them and allowing other substances to be washed away. A new rapid simplified NucliSens easyMAG-based approach is described and compared with the classical NucliSens easyMAG approach and with manual silica-based spin column purifications (Qiagen). The limit of detection (LOD) with the new rapid simplified NucliSens easyMAG approach was about 1PFU/1.5L against about 100PFU/1.5L using conventional sample treatments that included a concentration step using ultra-filtration.

Few-cycle laser driven reaction nanoscopy on aerosolized silica nanoparticles.

Nanoparticles offer unique properties as photocatalysts with large surface areas. Under irradiation with light, the associated near-fields can induce, enhance, and control molecular adsorbate reactions on the nanoscale. So far, however, there is no simple method available to spatially resolve the near-field induced reaction yield on the surface of nanoparticles. Here we close this gap by introducing reaction nanoscopy based on three-dimensional momentum-resolved photoionization. The technique is demonstrated for the spatially selective proton generation in few-cycle laser-induced dissociative ionization of ethanol and water on SiO2 nanoparticles, resolving a pronounced variation across the particle surface. The results are modeled and reproduced qualitatively by electrostatic and quasi-classical mean-field Mie Monte-Carlo (M3C) calculations. Reaction nanoscopy is suited for a wide range of isolated nanosystems and can provide spatially resolved ultrafast reaction dynamics on nanoparticles, clusters, and droplets.

Structural and functional neural correlates of vigilant and avoidant regulation style.

BACKGROUND: Regulation of emotional arousal is a relevant factor for mental health. The investigation of neural underpinnings of regulation styles in healthy individuals may provide important insights regarding potential risk factors. To fill the gap of structural correlates of regulation styles and to expand previous results, we focused on the association between brain structure, neural responsiveness and vigilant/avoidant regulation style. METHODS: In n = 302 healthy individuals regulation style was assessed with the Mainz Coping Inventory (MCI). Participants underwent structural and functional MRI during an emotion-processing paradigm. Structural MRI (voxel-based morphometry) and functional MRI were analysed in two regions of interest (amygdala and anterior cingulate cortex [ACC]). RESULTS: Regulation styles did not show an association with brain structure after correction for gender, age, trait anxiety, depressive symptoms. During emotion processing, a vigilant regulation style was negatively associated with ACC activation. LIMITATIONS: The cross-sectional study in a non-pathological sample is not adequate to unveil causalities or draw conclusions regarding prevention interventions. CONCLUSION: Regulation styles are associated with specific neural activation patterns. The association of a high-vigilant regulation style and low ACC activation during emotion processing in healthy participants might be a potential risk factor.

Social anhedonia in major depressive disorder: a symptom-specific neuroimaging approach.

While research concerning brain structural biomarkers of major depressive disorder (MDD) is continuously progressing, our state of knowledge regarding biomarkers of specific clinical profiles of MDD is still limited. The aim of the present study was to investigate brain structural correlates of social anhedonia as a cardinal symptom of MDD. In a cross-sectional study, we investigated n = 166 patients with MDD and n = 166 matched healthy controls (HC) using structural magnetic resonance imaging (MRI). Social anhedonia was assessed using the Chapman Scales for Social Anhedonia (SAS). An anhedonia x group ANCOVA was performed in a region of interest approach of the dorsal and ventral striatum (bilateral caudate nucleus, putamen, nucleus accumbens respectively) as well as on whole-brain level. The analyses revealed a significant main effect for social anhedonia: higher SAS-scores were associated with reduced gray matter volume in the bilateral caudate nucleus in both the MDD-group (pFWE = 0.002) and the HC-group (pFWE = 0.032). The whole-brain analysis confirmed this association (left: pFWE = 0.036, right: pFWE = 0.047). There was no significant main effect of group and no significant anhedonia x group interaction effect. This is the first study providing evidence for volumetric aberrations in the reward system related to social anhedonia independently of diagnosis, depression severity, medication status, and former course of disease. These results support the hypothesis that social anhedonia has a brain biomarker serving as a possible endophenotype of depression and possibly providing an alternative approach for a more precise and effective treatment.