Synaptoproteomic Analysis of the Prefrontal Cortex Reveals Spatio-Temporal Changes in SYNGAP1 Following Cannabinoid Exposure in Rat Adolescence.

The regular use of cannabis during adolescence has been associated with a number of negative life outcomes, including psychopathology and cognitive impairments. However, the exact molecular mechanisms that underlie these outcomes are just beginning to be understood. Moreover, very little is known about the spatio-temporal molecular changes that occur following cannabinoid exposure in adolescence.

The Retention of Older Employees and Core Work Activities: Evidence From Denmark.

Background And Objectives: Retention of older employees in the labor market is crucial to cope with aging populations. Retention of older employees can appear in different forms, such as phased retirement, bridge jobs, career development, or health promotion. However, little is known about how the offering of these retention strategies may vary across workplaces with different core work activities because the opportunities to implement different types of retention strategies are preconditioned by differences in the economic and labor market climate.

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine withdrawal but increases cocaine self-administration, cocaine-induced locomotor activity, and GluR1/GluA1 in the central nucleus of the amygdala in male cocaine-dependent rats.

Background: Cocaine addiction is a major public health problem. Despite decades of intense research, no effective treatments are available. Both preclinical and clinical studies strongly suggest that deep brain stimulation of the nucleus accumbens (NAcc) is a viable target for the treatment of cocaine use disorder (CUD).

Generic multicriteria approach to determine the best precipitation agent for removal of biomacromolecules prior to non-targeted metabolic analysis.

The removal of biomacromolecules from biofluids decreases the sample complexity and lower electrospray suppression effects. Furthermore, it can increase the analysis sensitivity, precision, and selectivity. Often removal approaches evaluate the model based on a single criterion, like protein removed or response of one of few specific metabolites.

Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological evidence demonstrating that cannabinoids can also alter the brain's initial molecular and epigenetic response to cocaine.

Educational differences in the influence of health on early work exit among older workers.

Objectives: Previous research has shown that poor physical and mental health are important risk factors for early work exit. We examined potential differences in this association in older workers (50+) across educational levels.

Methods: Coordinated analyses were carried out in longitudinal data sets from four European countries: the Netherlands (Longitudinal Aging Study Amsterdam), Denmark (Danish Longitudinal Study of Ageing), England (English Longitudinal Study of Ageing) and Germany (German Ageing Survey).

Educational inequalities in health after work exit: the role of work characteristics.

Background: Educational inequalities in health have been widely reported. A low educational level is associated with more adverse working conditions. Working conditions, in turn, are associated with health and there is evidence that this association remains after work exit.

Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.

Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1).

Perceived articulatory precision in patients with Parkinson's disease after deep brain stimulation of subthalamic nucleus and caudal zona incerta.

The effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and caudal zona incerta (cZi) on speech articulation in patients with Parkinson's disease (PD) was investigated. Read speech samples were collected from nine patients with STN-DBS and 10 with cZi-DBS. The recordings were made pre-operatively and 12 months post-operatively with stimulator on and off (on medication).

Hospitalisation patterns change over time in patients with atrial fibrillation.

Introduction: Atrial fibrillation (AF) is a cardiac epidemic. In this study, we aimed to describe the causes of hospital-isation in an AF population over time and to study how different AF treatment strategies affected hospitalization.

Material And Methods: This was an observational study in which long-term follow-up data were collected from hospital records, discharge papers and diagnostic codes.

Hydration and mobility of trehalose in aqueous solution.

The disaccharide trehalose stabilizes proteins against unfolding, but the underlying mechanism is not well understood. Because trehalose is preferentially excluded from the protein surface, it is of interest to examine how trehalose modifies the structure and dynamics of the solvent. From the spin relaxation rates of deuterated trehalose and (17)O-enriched water, we obtain the rotational dynamics of trehalose and water in solutions over wide ranges of concentration (0.

Rotational dynamics in supercooled water from nuclear spin relaxation and molecular simulations.

Structural dynamics in liquid water slow down dramatically in the supercooled regime. To shed further light on the origin of this super-Arrhenius temperature dependence, we report high-precision (17)O and (2)H NMR relaxation data for H(2)O and D(2)O, respectively, down to 37 K below the equilibrium freezing point. With the aid of molecular dynamics (MD) simulations, we provide a detailed analysis of the rotational motions probed by the NMR experiments.

Depression, anxiety and quality-of-life among relatives of patients with severe brain injury: the acute phase.

Primary Objective: To investigate the emotional well-being of relatives of patients with a severe brain injury in the acute setting, as well as risk factors associated with high anxiety and depression scores and impaired quality-of-life.

Research Design: Clinical convenience sample.

Methods And Procedures: Participants included 45 relatives of patients with severe brain injury recruited at a NICU.

Hydration dynamics of a halophilic protein in folded and unfolded states.

Proteins from halophilic microorganisms thriving at high salinity have an excess of charged carboxylate groups, and it is widely believed that this gives rise to an exceptionally strong hydration that stabilizes these proteins against unfolding and aggregation. Here, we examine this hypothesis by characterizing the hydration dynamics of a halophilic model protein with frequency- and temperature-dependent (17)O magnetic relaxation. The halophilic protein Kx6E was constructed by replacing six lysine residues with glutamate residues in the IgG binding domain of protein L.

The carbohydrate-binding site in galectin-3 is preorganized to recognize a sugarlike framework of oxygens: ultra-high-resolution structures and water dynamics.

The recognition of carbohydrates by proteins is a fundamental aspect of communication within and between living cells. Understanding the molecular basis of carbohydrate-protein interactions is a prerequisite for the rational design of synthetic ligands. Here we report the high- to ultra-high-resolution crystal structures of the carbohydrate recognition domain of galectin-3 (Gal3C) in the ligand-free state (1.

Structural dynamics of supercooled water from quasielastic neutron scattering and molecular simulations.

One of the outstanding challenges presented by liquid water is to understand how molecules can move on a picosecond time scale despite being incorporated in a three-dimensional network of relatively strong H-bonds. This challenge is exacerbated in the supercooled state, where the dramatic slowing down of structural dynamics is reminiscent of the, equally poorly understood, generic behavior of liquids near the glass transition temperature. By probing single-molecule dynamics on a wide range of time and length scales, quasielastic neutron scattering (QENS) can potentially reveal the mechanistic details of water's structural dynamics, but because of interpretational ambiguities this potential has not been fully realized.

High water mobility on the ice-binding surface of a hyperactive antifreeze protein.

Antifreeze proteins (AFPs) prevent uncontrolled ice formation in organisms exposed to subzero temperatures by binding irreversibly to specific planes of nascent ice crystals. To understand the thermodynamic driving forces and kinetic mechanism of AFP activity, it is necessary to characterize the hydration behavior of these proteins in solution. With this aim, we have studied the hyperactive insect AFP from Tenebrio molitor (TmAFP) with the (17)O magnetic relaxation dispersion (MRD) method, which selectively monitors the rotational motion and exchange kinetics of water molecules on picosecond-microsecond time scales.

Circulating levels of vasoactive peptides in patients with acute bacterial meningitis.

Purpose: The underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g.

Time scales of water dynamics at biological interfaces: peptides, proteins and cells.

Water 2H and 17O spin relaxation is used to study water dynamics in the hydration layers of two small peptides, two globular proteins and in living cells of two microorganisms. The dynamical heterogeneity of hydration water is characterized by performing relaxation measurements over a wide temperature range, extending deeply into the supercooled regime, or by covering a wide frequency range. Protein hydration layers can be described by a power-law distribution of rotational correlation times with an exponent close to 2.

Protein cold denaturation as seen from the solvent.

Unlike most ordered molecular systems, globular proteins exhibit a temperature of maximum stability, implying that the structure can be disrupted by cooling. This cold denaturation phenomenon is usually linked to the temperature-dependent hydrophobic driving force for protein folding. Yet, despite the key role played by protein-water interactions, hydration changes during cold denaturation have not been investigated experimentally.

Thermal signature of hydrophobic hydration dynamics.

Hydrophobic hydration, the perturbation of the aqueous solvent near an apolar solute or interface, is a fundamental ingredient in many chemical and biological processes. Both bulk water and aqueous solutions of apolar solutes behave anomalously at low temperatures for reasons that are not fully understood. Here, we use (2)H NMR relaxation to characterize the rotational dynamics in hydrophobic hydration shells over a wide temperature range, extending down to 243 K.

Dynamics at the protein-water interface from 17O spin relaxation in deeply supercooled solutions.

Most of the decisive molecular events in biology take place at the protein-water interface. The dynamical properties of the hydration layer are therefore of fundamental importance. To characterize the dynamical heterogeneity and rotational activation energy in the hydration layer, we measured the (17)O spin relaxation rate in dilute solutions of three proteins in a wide temperature range extending down to 238 K.

A dry ligand-binding cavity in a solvated protein.

Ligands usually bind to proteins by displacing water from the binding site. The affinity and kinetics of binding therefore depend on the hydration characteristics of the site. Here, we show that the extreme case of a completely dehydrated free binding site is realized for the large nonpolar binding cavity in bovine beta-lactoglobulin.

Virtual screening and bioassay study of novel inhibitors for dengue virus mRNA cap (nucleoside-2'O)-methyltransferase.

We report high-throughput structure-based virtual screening of putative Flavivirus 2'-O-methyltransferase inhibitors together with results from subsequent bioassay tests of selected compounds. Potential inhibitors for the S-adenosylmethionine binding site were explored using 2D similarity searching, pharmacophore filtering and docking. The inhibitory activities of 15 top-ranking compounds from the docking calculations were tested on a recombinant methyltransferase with the RNA substrate (7Me)GpppAC(5).

Is late stent thrombosis in drug-eluting stents a real clinical issue? A single-center experience and review of the literature.

Background: Randomized studies have not found an increased rate of late stent thrombosis (LAST) in drug-eluting stents (DES) compared with bare metal stents (BMS) but those studies were statistically not powered to show such a difference. At the same time there is an increasing number of reports of LAST in DES patients in the current literature.

Patients And Methods: We tried to describe the incidence of LAST in an unselected DES and BMS patient population.