Microspectroscopic SERS detection of interleukin-6 with rationally designed gold/silver nanoshells

Rationally designed gold/silver nanoshells (Au/Ag-NS) with plasmon resonances optimized for red laser excitation in order to minimize autofluorescence from clinical samples exhibit scattering cross-sections, which are ca. one order of magnitude larger compared with solid quasi-spherical gold nanoparticles (Au-NPs) of the same size. Hydrophilic stabilization and sterical accessibility for subsequent bioconjugation of Au/Ag-NS is achieved by coating their surface with a self-assembled monolayer (SAM) of rationally designed Raman reporter molecules comprising terminal mono- and tri-ethylene glycol (EG) spacers, respectively. The stability of the hydrophilically stabilized metal colloid was tested under different conditions. In contrast to metal colloids coated with a SAM without terminal EG spacers, the hydrophilically stabilized SERS particles do not aggregate under physiologically relevant conditions, i.e., buffer solutions with high ionic strength. Using these rationally designed SERS particles in conjunction with a microspectroscopic acquisition scheme, a sandwich immunoassay for the sensitive detection of interleukin-6 (IL-6) was developed. Several control experiments demonstrate the high specificity of the assay towards IL-6, with a lowest detectable concentration of ca. 1 pg mL -1. The signal strength of the Au/Ag-NS is at least one order of magnitude higher compared with hydrophilically stabilized, non-aggregated solid quasi-spherical Au-NPs of the same size. This journal i

Differential Kinetics of Aspergillus nidulans and Aspergillus fumigatus Phagocytosis

Acknowledgements: The authors would like to acknowledge Fraser P. Coxon and Ian Ganley for providing LC3-GFP-mCherry BMDMs. M.S.G. was supported by an FEMS research grant and F.L.v.d.V. was supported by ZonMW under the name EURO-CMC frame of E-Rare-2, the ERA-Net for Research on Rare Diseases.Peer reviewedPublisher PD

Social-specific impairment of negative emotion perception in alexithymia

Alexithymia has been characterized as an impaired ability of emotion processing and regulation. The definition of alexithymia does not include a social component. However, there is some evidence that social cognition may be compromised in individuals with alexithymia. Hence, emotional impairments associated with alexithymia may extend to socially relevant information. Here, we recorded electrophysiological responses of individuals meeting the clinically relevant cutoff for alexithymia (ALEX; n = 24) and individuals without alexithymia (NonALEX; n = 23) while they viewed affective scenes that varied on the dimensions of sociality and emotional valence during a rapid serial visual presentation task. We found that ALEX exhibited lower accuracy and larger N2 than NonALEX in the perception of social negative scenes. Source reconstruction revealed that the group difference in N2 was localized at the dorsal anterior cingulate cortex. Irrespective of emotional valence, ALEX showed stronger alpha power than NonALEX in social but not non-social conditions. Our findings support the hypothesis of social processing being selectively affected by alexithymia, especially for stimuli with negative valence. Electrophysiological evidence suggests altered deployment of attentional resources in the perception of social-specific emotional information in alexithymia. This work sheds light on the neuropsychopathology of alexithymia and alexithymia-related disorders

Connectome-Based Predictive Modeling of Individual Anxiety

Anxiety-related illnesses are highly prevalent in human society. Being able to identify neurobiological markers signaling high trait anxiety could aid the assessment of individuals with high risk for mental illness. Here, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity (rsFC) data to predict the degree of trait anxiety in 76 healthy participants. Using a computational "lesion" approach in CPM, we then examined the weights of the identified main brain areas as well as their connectivity. Results showed that the CPM successfully predicted individual anxiety based on whole-brain rsFC, especially the rsFC between limbic areas and prefrontal cortex. The prediction power of the model significantly decreased from simulated lesions of limbic areas, lesions of the connectivity within limbic areas, and lesions of the connectivity between limbic areas and prefrontal cortex. Importantly, this neural model generalized to an independent large sample (n = 501). These findings highlight important roles of the limbic system and prefrontal cortex in anxiety prediction. Our work provides evidence for the usefulness of connectome-based modeling in predicting individual personality differences and indicates its potential for identifying personality factors at risk for psychopathology

Spin Manipulation by Creation of Single-Molecule Radical Cations

All-trans-retinoic acid (ReA), a closed-shell organic molecule comprising only C, H, and O atoms, is investigated on a Au(111) substrate using scanning tunneling microscopy and spectroscopy. In dense arrays single ReA molecules are switched to a number of states, three of which carry a localized spin as evidenced by conductance spectroscopy in high magnetic fields. The spin of a single molecule may be reversibly switched on and off without affecting its neighbors. We suggest that ReA on Au is readily converted to a radical by the abstraction of an electron.Comment: 5 pages, 3 figures, accepted for publication in Phys. Rev. Let

Neurocomputational mechanisms underlying fear-biased adaptation learning in changing environments

AU Humans: Please confirm that all heading levels are represented correctly are able to adapt to the fast-changing world by estimating : statistical regularities of the environment. Although fear can profoundly impact adaptive behaviors, the computational and neural mechanisms underlying this phenomenon remain elusive. Here, we conducted a behavioral experiment (n = 21) and a functional magnetic resonance imaging experiment (n = 37) with a novel cue-biased adaptation learning task, during which we simultaneously manipulated emotional valence (fearful/neutral expressions of the cue) and environmental volatility (frequent/infrequent reversals of reward probabilities). Across 2 experiments, computational modeling consistently revealed a higher learning rate for the environment with frequent versus infrequent reversals following neutral cues. In contrast, this flexible adjustment was absent in the environment with fearful cues, suggesting a suppressive role of fear in adaptation to environmental volatility. This suppressive effect was underpinned by activity of the ventral striatum, hippocampus, and dorsal anterior cingulate cortex (dACC) as well as increased functional connectivity between the dACC and temporal-parietal junction (TPJ) for fear with environmental volatility. Dynamic causal modeling identified that the driving effect was located in the TPJ and was associated with dACC activation, suggesting that the suppression of fear on adaptive behaviors occurs at the early stage of bottom-up processing. These findings provide a neuro-computational account of how fear interferes with adaptation to volatility during dynamic environments.</p

Cardiotrophin-1 Induces Tumor Necrosis Factor α Synthesis in Human Peripheral Blood Mononuclear Cells

Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) α and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNFα in PBMC of healthy volunteers. CT-1 induced in PBMC TNFα protein in the supernatant and TNFα mRNA in a concentration- and time-dependent manner determined by ELISA and real-time PCR, respectively. Maximal TNFα protein was achieved with 100 ng/mL CT-1 after 3–6 hours and maximal TNFα mRNA induction after 1 hour. ELISA data were confirmed using immunofluorescent flow cytometry. Inhibitor studies with actinomycin D and brefeldin A showed that both protein synthesis and intracellular transport are essential for CT-1 induced TNFα expression. CT-1 caused a dose dependent nuclear factor (NF) κB translocation. Parthenolide inhibited both NFκB translocation and TNFα protein expression indicating that NFκB seems to be necessary. We revealed a new mechanism for elevated serum TNFα concentrations and PBMC activation in CHF besides the hypothesis of PBMC activation by bacterial translocation from the gut