Lipid-Chaperone Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins.

An increasing number of human diseases has been shown to be linked to aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, and α-synuclein are, indeed, involved in type-II diabetes, Alzheimer's, and Parkinson's, respectively. Despite the correlation of the toxicity of these proteins at early aggregation stages with membrane damage, the molecular events underlying the process is quite complex to understand.

Maintaining Safety in the Prison Environment: A Multilevel Analysis of Inmate Victimisation in Assaults.

Theoretical models of victimisation emphasise the importance of context. However, few studies have assessed the influence of prison environmental variables on inmate harm in physical assaults. This study used a multilevel model approach to examine individual- and facility-level factors associated with the incidence of assaults among inmates housed at correctional centres in New South Wales, Australia.

Symmetry-breaking transitions in the early steps of protein self-assembly.

Protein misfolding and subsequent self-association are complex, intertwined processes, resulting in development of a heterogeneous population of aggregates closely related to many chronic pathological conditions including Type 2 Diabetes Mellitus and Alzheimer's disease. To address this issue, here, we develop a theoretical model in the general framework of linear stability analysis. According to this model, self-assemblies of peptides with pronounced conformational flexibility may become, under particular conditions, unstable and spontaneously evolve toward an alternating array of partially ordered and disordered monomers.

Protein Adsorption at the Air-Water Interface by a Charge Sensing Interferometric Technique.

Protein uptake at the interface of a millimeter-sized air bubble in water is investigated by a recently developed differential interferometric technique. The technique allows the study of capillary waves with amplitudes around 10 m, excited at the surface of the bubble by an electric field of intensity on the order of 10 V/cm. When one studies the resonant modes of the bubble (radial and shape modes), it is possible to assess variations of interfacial properties and, in particular, of the net surface charge as a function of bulk protein concentration.

Helical Inclusions in Phospholipid Membranes: Lipid Adaptation and Chiral Order.

The lipid bilayer is a flexible matrix that is able to adapt in response to the perturbation induced by inclusions, such as peptides and proteins. Here we use molecular dynamics simulations with a coarse-grained model to investigate the effect of a helical inclusion on a lipid bilayer in the liquid disordered phase. We show that the helical inclusion induces a collective tilt of acyl chains, with a small, yet unambiguous difference between a right- and a left-handed inclusion.

Phospholipids Critical Micellar Concentrations Trigger Different Mechanisms of Intrinsically Disordered Proteins Interaction with Model Membranes.

Amyloidogenic proteins are involved in many diseases, including Alzheimer's, Parkinson's, and type II diabetes. These proteins are thought to be toxic for cells because of their abnormal interaction with the cell membrane. Simpler model membranes (LUVs) have been used to study the early steps of membrane-protein interactions and their subsequent evolution.

Chirality Enhancement of Porphyrin Supramolecular Assembly Driven by a Template Preorganization Effect.

Cationic polylysine promotes, under neutral conditions, the spontaneous aggregation of opposite charged ZnTPPS in water. Spectroscopic investigations evidence a different preorganization of ZnTPPS onto the polypeptide matrix depending on the chain length. Spinodal decomposition theory in confined geometry is used to model this mechanism by considering the time evolution of a homogeneous distribution of randomly adsorbed particles (porphyrins) onto a rodlike polyelectrolyte (polymer) of variable length L.

Nanometric Surface Oscillation Spectroscopy of Water-Poor Microemulsions.

Selectively exchanging metal complexes between emulsified water-poor microemulsions and concentrated solutions of mixed electrolytes is the core technology for strategic metal recycling. Nanostructuration triggered by solutes present in the organic phase is understood, but little is known about fluctuations of the microemulsion-water interface. We use here a modified version of an optoelectric device initially designed for air bubbles, in order to evidence resonant electrically induced surface waves of an oily droplet suspended in an aqueous phase.

An interferometric technique to study capillary waves.

We describe a new interferometric technique to study gas-liquid and liquid-liquid interfaces. Bubbles and drops are subjected to an alternating electric field which excites capillary oscillations at the interface, if charged. Bubble or drop deformation is detected by the change of the internal optical path of a laser beam crossing perpendicular to the oscillation axis.

Anomalous Behavior of Ultra-Low-Amplitude Capillary Waves. A Glimpse of the Viscoelastic Properties of Interfacial Water?

We investigate, both theoretically and by a differential interferometric technique, the behavior of large-wavelength capillary waves (of the order of 10 m) selectively excited at the surface of drops and bubbles with typical eigenfrequencies of the order of 10 Hz. The resonance peaks of gas bubbles or hydrocarbon drops in water (radius less than 1 mm) highlight anomalously small dissipation in the region of ultralow (sub-nanometric) oscillation amplitudes, reaching a plateau at higher amplitudes. This is in sharp contrast to the usual oscillating systems, where an anomalous behavior holds at large amplitudes alone.

Oscillations of Bubble Shape Cause Anomalous Surfactant Diffusion: Experiments, Theory, and Simulations.

We investigate, both theoretically and experimentally, the role played by the oscillations of the cell membrane on the capture rate of substances freely diffusing around the cell. To obtain quantitative results, we propose and build up a reproducible and tunable biomimetic experimental model system to simulate the phenomenon of an oscillation-enhanced (or depressed) capture rate (chemoreception) of a diffusant. The main advantage compared to real biological systems is that the different oscillation parameters (type of deformation, frequencies, and amplitudes) can be finely tuned.

Hospital admission for infection during early childhood influences developmental vulnerabilities at age 5 years.

Aim: Childhood infectious diseases can be associated with later physical and psychological ill health, and the effects of this association may be evident during early childhood development. This study aimed to examine the effects of hospitalisation for early life infection on early childhood development.

Methods: Hospital admission data for infection were obtained from the New South Wales Ministry of Health Admitted Patient Data Collection for 87 026 children, for whom the Australian Early Development Census (AEDC) was completed in their first year of formal schooling (age approximately 5 years).

Lipid-assisted protein transport: A diffusion-reaction model supported by kinetic experiments and molecular dynamics simulations.

The protein transport inside a cell is a complex phenomenon that goes through several difficult steps. The facilitated transport requires sophisticated machineries involving protein assemblies. In this work, we developed a diffusion-reaction model to simulate co-transport kinetics of proteins and lipids.

New South Wales Child Development Study (NSW-CDS): an Australian multiagency, multigenerational, longitudinal record linkage study.

Purpose: The initial aim of this multiagency, multigenerational record linkage study is to identify childhood profiles of developmental vulnerability and resilience, and to identify the determinants of these profiles. The eventual aim is to identify risk and protective factors for later childhood-onset and adolescent-onset mental health problems, and other adverse social outcomes, using subsequent waves of record linkage. The research will assist in informing the development of public policy and intervention guidelines to help prevent or mitigate adverse long-term health and social outcomes.

Trajectories of childhood internalizing and externalizing psychopathology and psychotic-like experiences in adolescence: A prospective population-based cohort study.

Adolescent internalizing and externalizing psychopathology is strongly associated with adult psychiatric morbidity, including psychotic disorders. This study examined whether internalizing or externalizing trajectories (continuity/discontinuity of symptoms) from middle childhood were associated with adolescent psychotic-like experiences (PLEs). Prospective data were collected from a community sample of 553 children (mean age = 10.

Do common genotypes of FK506 binding protein 5 (FKBP5) moderate the effects of childhood maltreatment on cognition in schizophrenia and healthy controls?

Common variants of the FK506 binding protein 5 (FKBP5) gene are implicated in psychotic and other disorders, via their role in regulating glucocorticoid receptor (GR) receptor sensitivity and effects on the broader function of the HPA system in response to stress. In this study, the effects of four FKBP5 polymorphisms (rs1360780, rs9470080, rs4713902, rs9394309) on IQ and eight other cognitive domains were examined in the context of exposure to childhood maltreatment in 444 cases with schizophrenia and 292 healthy controls (from a total sample of 617 cases and 659 controls obtained from the Australian Schizophrenia Research Bank; ASRB). Participants subjected to any kind of maltreatment (including physical, emotional, or sexual abuse or physical or emotional neglect) in childhood were classified as 'exposed'; cognitive functioning was measured with Repeatable Battery for the Assessment of Neuropsychological Status, the Controlled Oral Word Association Test, and IQ was estimated with the Weschler Test of Adult Reading.

Common or distinct pathways to psychosis? A systematic review of evidence from prospective studies for developmental risk factors and antecedents of the schizophrenia spectrum disorders and affective psychoses.

Background: Identifying the unique and shared premorbid indicators of risk for the schizophrenia spectrum disorders (SSD) and affective psychoses (AP) may refine aetiological hypotheses and inform the delivery of universal versus targeted preventive interventions. This systematic review synthesises the available evidence concerning developmental risk factors and antecedents of SSD and AP to identify those with the most robust support, and to highlight remaining evidence gaps.

Methods: A systematic search of prospective birth, population, high-risk, and case-control cohorts was conducted in Medline and supplemented by hand searching, incorporating published studies in English with full text available.

Trapping of Sodium Dodecyl Sulfate at the Air-Water Interface of Oscillating Bubbles.

We report that at very low initial bulk concentrations, a couple of hundred times below the critical micellar concentration (CMC), anionic surfactant sodium dodecyl sulfate (SDS) adsorbed at the air-water interface of a gas bubble cannot be removed, on the time scale of the experiment (hours), when the surrounding solution is gently replaced by pure water. Extremely sensitive interferometric measurements of the resonance frequency of the bubble-forced oscillations give precise access to the concentration of the surfactant monolayer. The bulk-interface dynamic exchange of SDS molecules is shown to be inhibited below a concentration which we believe refers to a kind of gas-liquid phase transition of the surface monolayer.

Resveratrol interferes with the aggregation of membrane-bound human-IAPP: a molecular dynamics study.

Amyloid aggregation of islet amyloid polypeptide (IAPP) in pancreatic tissues is a typical feature of type 2 diabetes mellitus. Resveratrol, a natural product extensively studied for its wide range of biological effects, has been shown to inhibit IAPP aggregation. However, the mechanism by which resveratrol inhibits IAPP aggregation is still far from complete elucidation.

Optimizing the crowding strategy: sugar-based ionic micelles in the dilute-to-condensed regime.

In the present study, we explore the effect of concentration on micelles made by different gangliosides, which are ionic biological glycolipids bearing multisugar headgroups with huge steric hindrance. Moreover, strong preferential interactions exist among like-conformer headgroups that can keep the ganglioside micelles in a trapped configuration. We extend the well-known ionic-amphiphiles paradigm, where local condensation and micelle crowding are matched by forming larger aggregates at increasing concentration.

Peptide-induced membrane curvature in edge-stabilized open bilayers: a theoretical and molecular dynamics study.

Peptide- or protein-induced curvatures of lipid membranes may be studied in molecular dynamics (MD) simulations. In these, membranes are usually modeled as infinitely extended bilayers by using periodic boundary conditions. However, the enforced periodicity results in an underestimation of the bending power of peptides, unless the patch size is much larger than the induced curvature radii.

Hydrodynamic enhancement of the diffusion rate in the region between two fluctuating membranes in close opposition: a theoretical and computational study.

Periodic variation of the distance between two weakly adhering bodies gives rise to a huge tangential motions of the sandwiched solvent layer (squeezing flow). Oscillations either can be induced by an external applied field or can spontaneously arise from the coupling with the solvent heat bath. First we calculated by the Navier-Stokes equation the components of the fluid velocity near two oscillating juxtaposed plates.

Comparing algorithms for deriving psychosis diagnoses from longitudinal administrative clinical records.

Purpose: Registers derived from administrative datasets are valuable tools in psychosis research, but diagnostic accuracy can be problematic. We sought to compare the relative performance of four methods for assigning a single diagnosis from longitudinal administrative clinical records when compared with reference diagnoses.

Methods: Diagnoses recorded in inpatient and community mental health records were compared to research diagnoses of psychotic disorders obtained from semi-structured clinical interviews for 289 persons.

Simulation of polyethylene glycol and calcium-mediated membrane fusion.

We report on the mechanism of membrane fusion mediated by polyethylene glycol (PEG) and Ca(2+) by means of a coarse-grained molecular dynamics simulation approach. Our data provide a detailed view on the role of cations and polymer in modulating the interaction between negatively charged apposed membranes. The PEG chains cause a reduction of the inter-lamellar distance and cause an increase in concentration of divalent cations.