Characterizing the Clinical Trajectory and Predicting Persistence and Deterioration of Attenuated Psychotic Symptoms in Ultra-High-Risk Individuals.

Background: Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR individuals with different clinical outcomes, and (3) whether non-remission (persistent APS or transition) can be predicted using baseline and/or longitudinal data.

Study Design: Participants were drawn from 2 randomized clinical trials: Neurapro (n = 220; discovery sample) and STEP (n = 180; external validation sample). First, 12-24 month symptoms and functioning were compared between UHR individuals with persistent APS, sustained remission, or transition to psychosis.

Stem Cell Markers LGR5, LGR4 and Their Immediate Signalling Partners are Dysregulated in Preeclampsia.

Leucine-rich repeat-containing G protein-coupled receptors 5/4 (LGR5/LGR4) are critical stem cell markers in epithelial tissues including intestine. They agonise wingless-related integration site (WNT) signalling. Until now, LGR5/LGR4 were uncharacterised in placenta, where analogous functions may exist.

Development of a Class A/B Hybrid GPCR System for the Proximity-Assisted Screening of GPCR Ligands.

Class A G protein-coupled receptors (GPCRs) are key mediators in numerous signaling pathways and important drug targets for several diseases. A major shortcoming in GPCR ligand screening is the detection limit for weak binding molecules, which is especially critical for poorly druggable GPCRs. Here, we present a proximity-based screening system for class A GPCRs, which adopts the natural two-step activation mechanism of class B GPCRs.

Structural Insights Into the Opening Mechanism of C1C2 Channelrhodopsin.

Channelrhodopsins, light-gated cation channels, enable precise control of neural cell depolarization or hyperpolarization with light in the field of optogenetics. This study integrates time-resolved serial crystallography and atomistic molecular dynamics (MD) simulations to resolve the structural changes during C1C2 channelrhodopsin activation. Our observations reveal that within the crystal environment, C1C2 predominantly remains in a light-activated state with characteristics of the M intermediate.

Frequency, redundancy, and context in bilingual acquisition.

We report findings from a corpus-based investigation of three young children growing up in German-English bilingual environments ( = 3;0, Range = 2;3-3;11). Based on 2,146,179 single words and two-word combinations in naturalistic child speech (CS) and child-directed speech (CDS), we assessed the degree to which the frequency distribution of CDS predicted CS usage over time, and systematically identified CS that was over- or underrepresented in the corpus with respect to matched CDS baselines. Results showed that CDS explained 61% of the variance in CS single-word use and 19.