Tripartite split-GFP assay to identify selective intracellular nanobody that suppresses GTPase RHOA subfamily downstream signaling.

Strategies based on intracellular expression of artificial binding domains present several advantages over manipulating nucleic acid expression or the use of small molecule inhibitors. Intracellularly-functional nanobodies can be considered as promising macrodrugs to study key signaling pathways by interfering with protein-protein interactions. With the aim of studying the RAS-related small GTPase RHOA family, we previously isolated, from a synthetic phage display library, nanobodies selective towards the GTP-bound conformation of RHOA subfamily proteins that lack selectivity between the highly conserved RHOA-like and RAC subfamilies of GTPases.

GluN2A and GluN2B NMDA receptors use distinct allosteric routes.

Allostery represents a fundamental mechanism of biological regulation that involves long-range communication between distant protein sites. It also provides a powerful framework for novel therapeutics. NMDA receptors (NMDARs), glutamate-gated ionotropic receptors that play central roles in synapse maturation and plasticity, are prototypical allosteric machines harboring large extracellular N-terminal domains (NTDs) that provide allosteric control of key receptor properties with impact on cognition and behavior.

Review of the effects of soft robotic gloves for activity-based rehabilitation in individuals with reduced hand function and manual dexterity following a neurological event.

Despite limited scientific evidence, there is an increasing interest in soft robotic gloves to optimize hand- and finger-related functional abilities following a neurological event. This review maps evidence on the effects and effectiveness of soft robotic gloves for hand rehabilitation and, whenever possible, patients' satisfaction. A systematized search of the literature was conducted using keywords structured around three areas: technology attributes, anatomy, and rehabilitation.

Unmasking GluN1/GluN3A excitatory glycine NMDA receptors.

GluN3A and GluN3B are glycine-binding subunits belonging to the NMDA receptor (NMDAR) family that can assemble with the GluN1 subunit to form unconventional receptors activated by glycine alone. Functional characterization of GluN1/GluN3 NMDARs has been difficult. Here, we uncover two modalities that have transformative properties on GluN1/GluN3A receptors.

An inter-dimer allosteric switch controls NMDA receptor activity.

NMDA receptors (NMDARs) are glutamate-gated ion channels that are key mediators of excitatory neurotransmission and synaptic plasticity throughout the central nervous system. They form massive heterotetrameric complexes endowed with unique allosteric capacity provided by eight extracellular clamshell-like domains arranged as two superimposed layers. Despite an increasing number of full-length NMDAR structures, how these domains cooperate in an intact receptor to control its activity remains poorly understood.

Prevalence, clinical correlates, and functional impact of subaortic ventricular septal bulge (from the Baltimore Longitudinal Study of Aging).

A localized hypertrophy of the subaortic segment of the ventricular septum-ventricular septal bulge (VSB)-has been frequently described in series of elderly population, but its prevalence with age, clinical correlates, and impact on cardiac function and exercise capacity remain uncertain. We explored these associations in a cross-sectional sample without known cardiac disease from the Baltimore Longitudinal Study of Aging. We randomly selected 700 participants (50% men, mean age 64 ± 15, range 26 to 95 years) and reviewed their echocardiograms.

Pulse wave velocity testing in the Baltimore longitudinal study of aging.

Carotid-femoral pulse wave velocity is considered the gold standard for measurements of central arterial stiffness obtained through noninvasive methods(1). Subjects are placed in the supine position and allowed to rest quietly for at least 10 min prior to the start of the exam. The proper cuff size is selected and a blood pressure is obtained using an oscillometric device.

Anatomy of the White Bear Suppression Inventory (WBSI): a review of previous findings and a new approach.

The White Bear Suppression Inventory (WBSI; Wegner & Zanakos, 1994) was originally designed to assess people's inclination toward thought suppression. In this article, we provide a detailed review of previous findings on the structure of this instrument and present a study that took a new statistical approach. It involved an exploratory factor analysis of the French WBSI using the weighted least squares mean and variance estimator as well as parametric item response theory analyses.

Depressive symptoms after trauma: is self-esteem a mediating factor?

Traumatic events have predicted depressive symptoms. Despite this consensus, it remains unclear as to whether the relationship between trauma and depression is consistently mediated by a negative cognitive schema, such as low self-esteem, or whether trauma influences mood independently of low self-esteem. This study tested these relationships while considering depressive symptom types.

Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: Neuropsychological and behavioral implications.

Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk for developing schizophrenia: half of affected adolescents report transient psychotic experiences and up to 30% of adults are diagnosed with schizophrenia. Prospective studies have shown that psychotic symptoms in childhood are predictive of later schizophreniform disorders.