Comparison analysis between standard polysomnographic data and in-ear-electroencephalography signals: a preliminary study.

Study Objectives: Polysomnography (PSG) currently serves as the benchmark for evaluating sleep disorders. Its discomfort makes long-term monitoring unfeasible, leading to bias in sleep quality assessment. Hence, less invasive, cost-effective, and portable alternatives need to be explored.

Impact of a clinical decision support system on paediatric drug dose prescribing: a randomised within-subject simulation trial.

Background: Drug dosing errors are among the most frequent causes of preventable harm in paediatrics. Due to the complexity of paediatric pharmacotherapy and the working conditions in healthcare, it is not surprising that human factor is a well-described source of error. Thus, a clinical decision support system (CDSS) that supports healthcare professionals (HCP) during the dose prescribing step provides a promising strategy for error prevention.

An Efficient Method of Expression and Purification of Amyloid-Beta (Aβ) Peptide from E. coli.

Amyloid-beta (Aβ) aggregation into soluble oligomers and fibril formation are associated with Alzheimer's disease (AD) pathogenesis. Aβ is the major form of the Aβ peptide present in neuritic plaques and shown to be neurotoxic both in vivo and in vitro. However, understanding the mechanism of its toxicity, aggregation, and other biochemical properties is limited because of its difficult production (recombinant or synthetic) and irreproducibility issues attributed to batch-to-batch preparation differences.

Basic Motor Competencies of 6- to 8-Year-Old Primary School Children in 10 European Countries: A Cross-Sectional Study on Associations With Age, Sex, Body Mass Index, and Physical Activity.

Basic motor competencies (BMC) are a prerequisite for children to be physically active, participate in sports and thus develop a healthy, active lifestyle. The present study provides a broad screening of BMC and associations with age, sex, body mass index (BMI) and extracurricular physical activity (PA) in 10 different European countries. The different country and regional contexts within Europe will offer a novel view on already established BMC associations.

Structure-function relationship of a novel fucoside-binding fruiting body lectin from Coprinopsis cinerea exhibiting nematotoxic activity.

Lectins are non-immunoglobulin-type proteins that bind to specific carbohydrate epitopes and play important roles in intra- and inter-organismic interactions. Here, we describe a novel fucose-specific lectin, termed CML1, which we identified from fruiting body extracts of Coprinopsis cinerea. For further characterization, the coding sequence for CML1 was cloned and heterologously expressed in Escherichia coli.

Visualization of Sparsely-populated Lower-order Oligomeric States of Human Mitochondrial Hsp60 by Cryo-electron Microscopy.

Human mitochondrial Hsp60 (mtHsp60) is a class I chaperonin, 51% identical in sequence to the prototypical E. coli chaperonin GroEL. mtHsp60 maintains the proteome within the mitochondrion and is associated with various neurodegenerative diseases and cancers.

Hepatitis A Virus Incidence Rates and Biomarker Dynamics for Plasma Donors, United States.

The United States is currently affected by widespread hepatitis A virus (HAV) outbreaks. We investigated HAV incidence rates among source plasma donors in the United States since 2016. Serial donations from HAV-positive frequent donors were analyzed for common biologic markers to obtain a detailed picture of the course of infection.

Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness.

l-2-Haloacid dehalogenases, industrially and environmentally important enzymes that catalyse cleavage of the carbon-halogen bond in S-2-halocarboxylic acids, were known to hydrolyse chlorinated, brominated and iodinated substrates but no activity towards fluorinated compounds had been reported. A screen for novel dehalogenase activities revealed four l-2-haloacid dehalogenases capable of defluorination. We now report crystal structures for two of these enzymes, Bpro0530 and Rha0230, as well as for the related proteins PA0810 and RSc1362, which hydrolyse chloroacetate but not fluoroacetate, all at ∼2.

Description of a clinical decision support tool with integrated dose calculator for paediatrics.

Medication errors, especially dosing errors are a leading cause of preventable harm in paediatric patients. The paediatric patient population is particularly vulnerable to dosing errors due to immaturity of metabolising organs and developmental changes. Moreover, the lack of clinical trial data or suitable drug forms, and the need for weight-based dosing, does not simplify drug dosing in paediatric or neonatal patients.

Probing the Interaction of Huntingtin Exon-1 Polypeptides with the Chaperonin Nanomachine GroEL.

Huntington's disease arises from polyQ expansion within the exon-1 region of huntingtin (htt ), resulting in an aggregation-prone protein that accumulates in neuronal inclusion bodies. We investigate the interaction of various htt constructs with the bacterial analog (GroEL) of the human chaperonin Hsp60. Using fluorescence spectroscopy and electron and atomic force microscopy, we show that GroEL inhibits fibril formation.

A weakened interface in the P182L variant of HSP27 associated with severe Charcot-Marie-Tooth neuropathy causes aberrant binding to interacting proteins.

HSP27 is a human molecular chaperone that forms large, dynamic oligomers and functions in many aspects of cellular homeostasis. Mutations in HSP27 cause Charcot-Marie-Tooth (CMT) disease, the most common inherited disorder of the peripheral nervous system. A particularly severe form of CMT disease is triggered by the P182L mutation in the highly conserved IxI/V motif of the disordered C-terminal region, which interacts weakly with the structured core domain of HSP27.

The three-dimensional structure of human β-endorphin amyloid fibrils.

In the pituitary gland, hormones are stored in a functional amyloid state within acidic secretory granules before they are released into the blood. To gain a detailed understanding of the structure-function relationship of amyloids in hormone secretion, the three-dimensional (3D) structure of the amyloid fibril of the human hormone β-endorphin was determined by solid-state NMR. We find that β-endorphin fibrils are in a β-solenoid conformation with a protonated glutamate residue in their fibrillar core.

Assessing Rhythmic Visual Entrainment and Reinstatement of Brain Oscillations to Modulate Memory Performance.

The human brain's ability to store information and remember past events is thought to be orchestrated by the synchronization of neuronal oscillations in various frequency bands. A vast amount of research has found that neural oscillations in the theta (∼4-7 Hz) and alpha (∼8-12 Hz) bands play an important role in memory formation. More specifically, it has been suggested that memory performance benefits if the same oscillatory pattern is present during encoding and retrieval.

Reinstating verbal memories with virtual contexts: Myth or reality?

When learning new information, contextual information about the encoding situation is stored in addition to the focal memory content. Later, these strings of extra information can help retrieve the learned content as demonstrated by experiments where contextual cues from an encoding situation facilitate remembering and improve memory performance when reinstated during retrieval. This context-dependent memory effect has been investigated over the course of several decades and has been demonstrated with many different types of contexts.

Probing the mechanism of inhibition of amyloid-β(1-42)-induced neurotoxicity by the chaperonin GroEL.

The human chaperonin Hsp60 is thought to play a role in the progression of Alzheimer's disease by mitigating against intracellular β-amyloid stress. Here, we show that the bacterial homolog GroEL (51% sequence identity) reduces the neurotoxic effects of amyloid-β(1-42) (Aβ42) on human neural stem cell-derived neuronal cultures. To understand the mechanism of GroEL-mediated abrogation of neurotoxicity, we studied the interaction of Aβ42 with GroEL using a variety of biophysical techniques.

Extensive Sampling of the Cavity of the GroEL Nanomachine by Protein Substrates Probed by Paramagnetic Relaxation Enhancement.

The chaperonin GroEL is a 800 kDa nanomachine comprising two heptameric rings, each of which encloses a large cavity or folding chamber. The GroEL cycle involves ATP-dependent capping of the cavity by the cochaperone GroES to create a nanocage in which a single protein molecule can fold. We investigate how protein substrates sample the cavity prior to encapsulation by GroES using paramagnetic relaxation enhancement to detect transient, sparsely populated interactions between apo GroEL, paramagnetically labeled at several sites within the cavity, and three variants of an SH3 protein domain (the fully native wild type, a triple mutant that exchanges between a folded state and an excited folding intermediate, and a stable folding intermediate mimetic).

Binding of Polythiophenes to Amyloids: Structural Mapping of the Pharmacophore.

Luminescent conjugated polythiophenes bind to amyloid proteins with high affinity. Their fluorescence properties, which are modulated by the detailed conformation in the bound state, are highly sensitive to structural features of the amyloid. Polythiophenes therefore represent diagnostic markers for the detection and differentiation of pathological amyloid aggregates.

Disassembly/reassembly strategy for the production of highly pure GroEL, a tetradecameric supramolecular machine, suitable for quantitative NMR, EPR and mutational studies.

GroEL, a prototypical member of the chaperonin class of chaperones, is a large supramocular machine that assists protein folding and plays an important role in proteostasis. GroEL comprises two heptameric rings, each of which encloses a large cavity that provides a folding chamber for protein substrates. Many questions remain regarding the mechanistic details of GroEL facilitated protein folding.

Chaperonin GroEL accelerates protofibril formation and decorates fibrils of the Het-s prion protein.

We have studied the interaction of the prototypical chaperonin GroEL with the prion domain of the Het-s protein using solution and solid-state NMR, electron and atomic force microscopies, and EPR. While GroEL accelerates Het-s protofibril formation by several orders of magnitude, the rate of appearance of fibrils is reduced. GroEL remains bound to Het-s throughout the aggregation process and densely decorates the fibrils at a regular spacing of ∼200 Å.

Fast NMR-Based Determination of the 3D Structure of the Binding Site of Protein-Ligand Complexes with Weak Affinity Binders.

In early drug discovery approaches, screening hits are often weak affinity binders that are difficult to characterize in structural detail, particularly towards obtaining the 3D structure of protein-ligand complexes at atomic resolution. NMR is the outstanding technique to tackle such problems, yet suffers from a tedious structure calculation process. NMR was recently developed to alleviate the laborious element of routine NMR structure calculation procedures and provides the structural information at protein-ligand interaction sites orders of magnitude faster than standard procedures.

Quenched hydrogen-deuterium exchange NMR of a disease-relevant Aβ(1-42) amyloid polymorph.

Alzheimer's disease is associated with the aggregation into amyloid fibrils of Aβ(1-42) and Aβ(1-40) peptides. Interestingly, these fibrils often do not obtain one single structure but rather show different morphologies, so-called polymorphs. Here, we compare quenched hydrogen-deuterium (H/D) exchange of a disease-relevant Aβ(1-42) fibril for which the 3D structure has been determined by solid-state NMR with H/D exchange previously determined on another structural polymorph.

Long Distance Measurements up to 160 Å in the GroEL Tetradecamer Using Q-Band DEER EPR Spectroscopy.

Current distance measurements between spin-labels on multimeric protonated proteins using double electron-electron resonance (DEER) EPR spectroscopy are generally limited to the 15-60 Å range. Here we show how DEER experiments can be extended to dipolar evolution times of ca. 80 μs, permitting distances up to 170 Å to be accessed in multimeric proteins.

Atomic-resolution structure of a disease-relevant Aβ(1-42) amyloid fibril.

Amyloid-β (Aβ) is present in humans as a 39- to 42-amino acid residue metabolic product of the amyloid precursor protein. Although the two predominant forms, Aβ(1-40) and Aβ(1-42), differ in only two residues, they display different biophysical, biological, and clinical behavior. Aβ(1-42) is the more neurotoxic species, aggregates much faster, and dominates in senile plaque of Alzheimer's disease (AD) patients.

Solid-state NMR sequential assignment of an Amyloid-β(1-42) fibril polymorph.

The formation of fibrils of the amyloid-β (Aβ) peptide is considered to be a key event in the pathology of Alzheimer's disease (AD). The determination of a high-resolution structure of these fibrils is relevant for the understanding of the molecular basis of AD. In this work, we present the sequential resonance assignment of one of the polymorphs of Aβ(1-42) fibrils.