SleepSync: Early Testing of a Personalised Sleep-Wake Management Smartphone Application for Improving Sleep and Cognitive Fitness in Defence Shift Workers.

Shift work, long work hours, and operational tasks contribute to sleep and circadian disruption in defence personnel, with profound impacts on cognition. To address this, a digital technology, the SleepSync app, was designed for use in defence. A pre-post design study was undertaken to examine whether four weeks app use improved sleep and cognitive fitness (high performance neurocognition) in a cohort of shift workers from the Royal Australian Air Force.

Pilot feasibility testing of biomathematical model recommendations for personalising sleep timing in shift workers.

Sleep disturbances and circadian disruption play a central role in adverse health, safety, and performance outcomes in shift workers. While biomathematical models of sleep and alertness can be used to personalise interventions for shift workers, their practical implementation is undertested. This study tested the feasibility of implementing two biomathematical models-the Phillips-Robinson Model and the Model for Arousal Dynamics-in 28 shift-working nurses, 14 in each group.

Prediction of shiftworker alertness, sleep, and circadian phase using a model of arousal dynamics constrained by shift schedules and light exposure.

Study Objectives: The study aimed to, for the first time, (1) compare sleep, circadian phase, and alertness of intensive care unit (ICU) nurses working rotating shifts with those predicted by a model of arousal dynamics; and (2) investigate how different environmental constraints affect predictions and agreement with data.

Methods: The model was used to simulate individual sleep-wake cycles, urinary 6-sulphatoxymelatonin (aMT6s) profiles, subjective sleepiness on the Karolinska Sleepiness Scale (KSS), and performance on a Psychomotor Vigilance Task (PVT) of 21 ICU nurses working day, evening, and night shifts. Combinations of individual shift schedules, forced wake time before/after work and lighting, were used as inputs to the model.

NFTsim: Theory and Simulation of Multiscale Neural Field Dynamics.

A user ready, portable, documented software package, NFTsim, is presented to facilitate numerical simulations of a wide range of brain systems using continuum neural field modeling. NFTsim enables users to simulate key aspects of brain activity at multiple scales. At the microscopic scale, it incorporates characteristics of local interactions between cells, neurotransmitter effects, synaptodendritic delays and feedbacks.

Relating Alpha Power and Phase to Population Firing and Hemodynamic Activity Using a Thalamo-cortical Neural Mass Model.

Oscillations are ubiquitous phenomena in the animal and human brain. Among them, the alpha rhythm in human EEG is one of the most prominent examples. However, its precise mechanisms of generation are still poorly understood.

Mathematical framework for large-scale brain network modeling in The Virtual Brain.

In this article, we describe the mathematical framework of the computational model at the core of the tool The Virtual Brain (TVB), designed to simulate collective whole brain dynamics by virtualizing brain structure and function, allowing simultaneous outputs of a number of experimental modalities such as electro- and magnetoencephalography (EEG, MEG) and functional Magnetic Resonance Imaging (fMRI). The implementation allows for a systematic exploration and manipulation of every underlying component of a large-scale brain network model (BNM), such as the neural mass model governing the local dynamics or the structural connectivity constraining the space time structure of the network couplings. Here, a consistent notation for the generalized BNM is given, so that in this form the equations represent a direct link between the mathematical description of BNMs and the components of the numerical implementation in TVB.

Integrating neuroinformatics tools in TheVirtualBrain.

TheVirtualBrain (TVB) is a neuroinformatics Python package representing the convergence of clinical, systems, and theoretical neuroscience in the analysis, visualization and modeling of neural and neuroimaging dynamics. TVB is composed of a flexible simulator for neural dynamics measured across scales from local populations to large-scale dynamics measured by electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), and core analytic and visualization functions, all accessible through a web browser user interface. A datatype system modeling neuroscientific data ties together these pieces with persistent data storage, based on a combination of SQL and HDF5.

The Virtual Brain: a simulator of primate brain network dynamics.

We present The Virtual Brain (TVB), a neuroinformatics platform for full brain network simulations using biologically realistic connectivity. This simulation environment enables the model-based inference of neurophysiological mechanisms across different brain scales that underlie the generation of macroscopic neuroimaging signals including functional MRI (fMRI), EEG and MEG. Researchers from different backgrounds can benefit from an integrative software platform including a supporting framework for data management (generation, organization, storage, integration and sharing) and a simulation core written in Python.

The effects of physiologically plausible connectivity structure on local and global dynamics in large scale brain models.

Functionally relevant large scale brain dynamics operates within the framework imposed by anatomical connectivity and time delays due to finite transmission speeds. To gain insight on the reliability and comparability of large scale brain network simulations, we investigate the effects of variations in the anatomical connectivity. Two different sets of detailed global connectivity structures are explored, the first extracted from the CoCoMac database and rescaled to the spatial extent of the human brain, the second derived from white-matter tractography applied to diffusion spectrum imaging (DSI) for a human subject.

Small-world properties of nonlinear brain activity in schizophrenia.

A disturbance in the interactions between distributed cortical regions may underlie the cognitive and perceptual dysfunction associated with schizophrenia. In this article, nonlinear measures of cortical interactions and graph-theoretical metrics of network topography are combined to investigate this schizophrenia "disconnection hypothesis." This is achieved by analyzing the spatiotemporal structure of resting state scalp EEG data previously acquired from 40 young subjects with a recent first episode of schizophrenia and 40 healthy matched controls.

CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45.

CDX2 is a Drosophila caudal-related homeobox transcription factor that is expressed specifically in the intestine. In mice, ectopic expression of CDX2 in the gastric mucosa gives rise to intestinal metaplasia and in one model, gastric carcinoma. In humans, increased CDX2 expression is associated with gastric intestinal metaplasia and tubular adenocarcinomas.

CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48.

CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. CDX2 is a marker of colon cancer, with strong staining in up to 90% of colonic adenocarcinomas. CDX2 heterozygous-null mice develop colonic neoplasms, which have suggested that CDX2 is a tumor suppressor.

Molecular cloning and cellular localization of a furin-like prohormone convertase from the atrial gland of Aplysia.

Prohormone convertases (PCs) are Ca(2+)-dependent subtilisin-related endoproteases that have been implicated in the post-translational processing of prohormones and other proproteins. Furin is an ubiquitously expressed PC that has been shown to hydrolyze a wide variety of precursor proteins in secretory pathways. We have screened an Aplysia atrial gland cDNA library using a furin probe prepared by polymerase chain reaction (PCR) and have isolated an Aplysia furin-related 6.

Molecular cloning, cDNA sequence, and localization of a prohormone convertase (PC2) from the Aplysia atrial gland.

Neuropeptides and peptide hormones are synthesized as part of larger precursor proteins that are processed post-translationally by subtilisin-related calcium-dependent prohormone convertases (PCs), frequently at multiple basic sites, to generate biologically active peptides. The atrial gland of Aplysia californica produces large quantities of egg-laying hormone (ELH)-related peptides, providing a unique opportunity to study prohormone processing. We have screened an Aplysia atrial gland cDNA library using a Lymnaea stagnalis PC2 probe and have isolated an Aplysia PC2-related 4.

Structural characterization of a Lymnaea putative endoprotease related to human furin.

A number of peptides have been identified in the central nervous system of the freshwater snail, Lymnaea stagnalis, that function as hormones and neurotransmitters/neuromodulators. These peptides are typically proteolytically processed from larger prohormones mostly at sites composed of single or multiple basic amino acid residues. Previously we demonstrated a diversity of putative prohormone convertases that may be involved in prohormone processing in the Lymnaea brain.

Occurrence of a furin-like prohormone processing enzyme in Aplysia neuroendocrine bag cells.

1. Strong evidence is accumulating that the endoproteases which process prohormones at dibasic residue cleavage sites are members of a subtilisin-related class of proteases. 2.

Kinetic analysis of biotinylation of specific residues of peptides by high-performance liquid chromatography.

A procedure employing C18 reversed-phase high-performance liquid chromatography (HPLC) is described for evaluating the kinetics of biotinylation of specific residues of peptides after reaction with N-hydroxysuccinimide esters of biotin. Utilizing this HPLC method, we determined the observed pseudo-first-order reaction rate constant (k'1) of biotinylation of lysyl residues in two model peptides, [biotinyl-Ser108]ProA-egg laying hormone (108-121) and pGlu-Lys-Trp-Ala-Pro, to be 1.22.

N-acylation of Aplysia egg-laying hormone with biotin. Characterization of bioactive and inactive derivatives.

Chemical modification of the egg-laying hormone (ELH) of Aplysia by reaction with the N-hydroxysuccinimide ester of biotin, which contained 6-aminohexanoic acid as spacer, yielded seven distinct derivatives that were readily separated by reversed-phase high performance liquid chromatography. The derivatives were chemically characterized by amino acid compositional analysis, sequence analysis, and mass spectrometry. The seven derivatives resulted from combinations of differential modification of the three amino groups in the ELH molecule located at Ile1 (alpha-NH2), Lys8, and Lys36.

Biotinylated peptides/proteins. I. Determination of stoichiometry of derivatization.

A method is described for the determination of the stoichiometry of biotinylation of peptides and proteins after reaction with an N-hydroxysuccinimide ester of biotin containing the extended spacer arm 6-aminohexanoic acid (NHS-epsilon Ahx-biotin). The method of analysis, based on the quantification of phenylthiocarbamyl derivatives of 6-aminohexanoic acid, is able to measure low picomolar amounts of biotinyl derivative. Analyses were performed using an automated on-line hydrolyzer-derivatizer followed by high-performance liquid chromatography.

Aplysia brasiliana neurons R3-R14: primary structure of the myoactive histidine-rich basic peptide and its prohormone.

Neurons R3-R14 of the marine mollusc Aplysia are model neuroendocrine cells thought to regulate cardiovascular activity in vivo. The cells express a gene encoding three peptides--peptides I, II and the histidine-rich basic peptide (HRBP)--each of which has been chemically characterized in Aplysia californica. In the studies presented here, HRBP and its prohormone (proHRBP) were purified from A.

Aplysia californica neurons R3-R14: primary structure of the myoactive histidine-rich basic peptide and peptide I.

The R3-R14 neurons of the marine mollusc Aplysia are neuroendocrine cells that express a gene encoding peptides I, II and histidine-rich basic peptide (HRBP), a myoactive peptide that excites Aplysia heart and enhances gut motility in vitro. Peptide II has been chemically characterized (35), but the complete primary structures of peptide I and HRBP have not been established by amino acid sequence analysis. HRBP, peptide I, and the prohormone (proHRBP) were therefore purified from acid extracts of Aplysia californica neural tissue using sequential gel filtration and reverse-phase high-performance liquid chromatography and chemically characterized.