The utility of wearable headband electroencephalography and pulse photoplethysmography to assess cortical and physiological arousal in individuals with stress-related mental disorders.

Several stress-related mental disorders are characterised by disturbed sleep, but objective sleep biomarkers are not routinely examined in psychiatric patients. We examined the use of wearable-based sleep biomarkers in a psychiatric sample with headband electroencephalography (EEG) including pulse photoplethysmography (PPG), with an additional focus on microstructural elements as especially the shift from low to high frequencies appears relevant for several stress-related mental disorders. We analysed 371 nights of sufficient quality from 83 healthy participants and those with a confirmed stress-related mental disorder (anxiety-affective spectrum).

Facing Your Fear in Immersive Virtual Reality: Avoidance Behavior in Specific Phobia.

Specific phobias are the most common anxiety disorder and are characterized by avoidance behavior. Avoidance behavior impacts daily function and is proposed to impair extinction learning. However, despite its prevalence, its objective assessment remains a challenge.

Examining Differences in Fear Learning in Patients With Obsessive-Compulsive Disorder With Pupillometry, Startle Electromyography and Skin Conductance Responses.

Obsessive-compulsive disorder (OCD) is characterized by recurrent, persistent thoughts and repetitive behaviors causing stress and anxiety. In the associative learning model of OCD, mechanisms of fear extinction are supposed to partly underlie symptom development, maintenance and treatment of OCD, proposing that OCD patients suffer from rigid memory associations and inhibitory learning deficits. To test these assumptions, previous studies have used skin conductance and subjective ratings as readouts in fear conditioning paradigms, finding impaired fear extinction learning, impaired fear extinction recall or no differences between individuals with OCD and healthy controls.

Pupillometry tracks cognitive load and salience network activity in a working memory functional magnetic resonance imaging task.

The diameter of the human pupil tracks working memory processing and is associated with activity in the frontoparietal network. At the same time, recent neuroimaging research has linked human pupil fluctuations to activity in the salience network. In this combined functional magnetic resonance imaging (fMRI)/pupillometry study, we recorded the pupil size of healthy human participants while they performed a blockwise organized working memory task (N-back) inside an MRI scanner in order to monitor the pupil fluctuations associated neural activity during working memory processing.

Structural correlates of trauma-induced hyperarousal in mice.

Post-traumatic stress disorder (PTSD) is a chronic disease caused by traumatic incidents. Numerous studies have revealed grey matter volume differences in affected individuals. The nature of the disease renders it difficult to distinguish between a priori versus a posteriori changes.

Exploratory drive, fear, and anxiety are dissociable and independent components in foraging mice.

Anxiety-like behavior of rodents is frequently accompanied by reduced exploration. Here, we identify dissociable components of anxiety, fear, and exploratory drive of sated and foraging mice. With the help of behavioral assays, including the open field task, elevated plus maze, dark-light transition task, and beetle mania task, we demonstrate a general increase in exploration by food restriction.

Quantifying Human Avoidance Behavior in Immersive Virtual Reality.

Avoidance behavior is a key symptom of most anxiety disorders and a central readout in animal research. However, the quantification of real-life avoidance behavior in humans is typically restricted to clinical populations, who show actual avoidance of phobic objects. In experimental approaches for healthy participants, many avoidance tasks utilize button responses or a joystick navigation on the screen as indicators of avoidance behavior.

No robust differences in fear conditioning between patients with fear-related disorders and healthy controls.

Fear conditioning and extinction serve as a dominant model for the development and maintenance of pathological anxiety, particularly for phasic fear to specific stimuli or situations. The validity of this model would be supported by differences in the physiological or subjective fear response between patients with fear-related disorders and healthy controls, whereas the model's validity would be questioned by a lack of such differences. We derived pupillometry, skin conductance response and startle electromyography as well as unconditioned stimulus expectancy in a two-day fear acquisition, immediate extinction and recall task and compared an unmedicated group of patients (n = 73) with phobias or panic disorder and a group of patients with posttraumatic stress disorder (PTSD, n = 21) to a group of carefully screened healthy controls (n = 35).

E-selectin ligand complexes adopt an extended high-affinity conformation.

E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewis(x) (sLe(x)). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lifetime of E-selectin/ligand complexes under tensile force in a so-called catch-bond binding mode. Co-crystal structures of a representative fragment of the extracellular E-selectin region with sLe(x) and a glycomimetic antagonist thereof reveal an extended E-selectin conformation, which is identified as a high-affinity binding state of E-selectin by molecular dynamics simulations.

Implications of the E-selectin S128R mutation for drug discovery.

The C-type lectin E-selectin mediates the rolling of circulating leukocytes on vascular endothelial cells during the inflammatory process. In numerous studies, the S128R mutation of the E-selectin was associated with cardiovascular and autoimmune diseases. There is evidence that the S128R E-selectin mutation leads to a loss in ligand specificity, thus increasing leukocyte recruitment.

Sialyl Lewis(x): a "pre-organized water oligomer"?

Organized and released: Sialyl Lewis(x) (sLe(x)) represents a "pre-organized water oligomer", that is, a surrogate for clustered water molecules attached to a scaffold. The impetus for sLe(x) binding to E-selectin is shown to be the high degree of pre-organization allowing an array of directed hydrogen bonds, and the entropic benefit of the release of water molecules from the large binding interface to bulk water (see picture).

Pre-organization of the core structure of E-selectin antagonists.

A new class of N-acetyl-D-glucosamine (GlcNAc) mimics for E-selectin antagonists was designed and synthesized. The mimic consists of a cyclohexane ring substituted with alkyl substituents adjacent to the linking position of the fucose moiety. Incorporation into E-selectin antagonists led to the test compounds 8 and the 2'-benzoylated analogues 21, which exhibit affinities in the low micromolar range.

E- and P-selectin: differences, similarities and implications for the design of P-selectin antagonists.

Selectins form a family of Ca2+ -dependent carbohydrate binding proteins that mediate the initial step of leukocyte recruitment in the inflammatory process. Blocking of selectins is therefore considered a promising therapeutic approach to treat acute and chronic inflammatory diseases which are caused by excessive extravasation of leukocytes. This mini-review highlights the major structural differences between E- and P-selectin and summarizes the resulting strategies for the design of selectin antagonists.