Exploring global and local processes underlying alterations in resting-state functional connectivity and dynamics in schizophrenia.

Introduction: We examined changes in large-scale functional connectivity and temporal dynamics and their underlying mechanisms in schizophrenia (ScZ) through measurements of resting-state functional magnetic resonance imaging (rs-fMRI) data and computational modelling.

Methods: The rs-fMRI measurements from patients with chronic ScZ (n=38) and matched healthy controls (n=43), were obtained through the public schizConnect repository. Computational models were constructed based on diffusion-weighted MRI scans and fit to the experimental rs-fMRI data.

Attention Mechanisms in Clinical Text Classification: A Comparative Evaluation.

Attention mechanisms are now a mainstay architecture in neural networks and improve the performance of biomedical text classification tasks. In particular, models that perform automated medical encoding of clinical documents make extensive use of the label-wise attention mechanism. A label-wise attention mechanism increases a model's discriminatory ability by using label-specific reference information.

Extracellular Vesicles and Their Membranes: Exosomes vs. Virus-Related Particles.

Cells produce nanosized lipid membrane-enclosed vesicles which play important roles in intercellular communication. Interestingly, a certain type of extracellular vesicle, termed exosomes, share physical, chemical, and biological properties with enveloped virus particles. To date, most similarities have been discovered with lentiviral particles, however, other virus species also frequently interact with exosomes.

40-Hz Auditory Steady-State Responses in Schizophrenia: Toward a Mechanistic Biomarker for Circuit Dysfunctions and Early Detection and Diagnosis.

There is converging evidence that 40-Hz auditory steady-state responses (ASSRs) are robustly impaired in schizophrenia and could constitute a potential biomarker for characterizing circuit dysfunctions as well as enable early detection and diagnosis. Here, we provide an overview of the mechanisms involved in 40-Hz ASSRs, drawing on computational, physiological, and pharmacological data with a focus on parameters modulating the balance between excitation and inhibition. We will then summarize findings from electro- and magnetoencephalographic studies in participants at clinical high risk for psychosis, patients with first-episode psychosis, and patients with schizophrenia to identify the pattern of deficits across illness stages, the relationship with clinical variables, and the prognostic potential.

The effect of alterations of schizophrenia-associated genes on gamma band oscillations.

Abnormalities in the synchronized oscillatory activity of neurons in general and, specifically in the gamma band, might play a crucial role in the pathophysiology of schizophrenia. While these changes in oscillatory activity have traditionally been linked to alterations at the synaptic level, we demonstrate here, using computational modeling, that common genetic variants of ion channels can contribute strongly to this effect. Our model of primary auditory cortex highlights multiple schizophrenia-associated genetic variants that reduce gamma power in an auditory steady-state response task.

Synchronization Through Uncorrelated Noise in Excitatory-Inhibitory Networks.

Gamma rhythms play a major role in many different processes in the brain, such as attention, working memory, and sensory processing. While typically considered detrimental, counterintuitively noise can sometimes have beneficial effects on communication and information transfer. Recently, Meng and Riecke showed that synchronization of interacting networks of inhibitory neurons in the gamma band (i.

The beta component of gamma-band auditory steady-state responses in patients with schizophrenia.

The mechanisms underlying circuit dysfunctions in schizophrenia (SCZ) remain poorly understood. Auditory steady-state responses (ASSRs), especially in the gamma and beta band, have been suggested as a potential biomarker for SCZ. While the reduction of 40 Hz power for 40 Hz drive has been well established and replicated in SCZ patients, studies are inconclusive when it comes to an increase in 20 Hz power during 40 Hz drive.

Structural Differences Between Healthy Subjects and Patients With Schizophrenia or Schizoaffective Disorder: A Graph and Control Theoretical Perspective.

The coordinated dynamic interactions of large-scale brain circuits and networks have been associated with cognitive functions and behavior. Recent advances in network neuroscience have suggested that the anatomical organization of such networks puts fundamental constraints on the dynamical landscape of brain activity, i.e.

On the Relationship of Viral Particles and Extracellular Vesicles: Implications for Viral Vector Technology.

Gene therapy vectors derived from different viral species have become a fixture in biomedicine, both for direct therapeutic intervention and as tools to facilitate cell-based therapies, such as chimeric antigen receptor-based immunotherapies. On the contrary, extracellular vesicles have only recently gained a massive increase in interest and, concomitantly, knowledge in the field has drastically risen. Viral infections and extracellular vesicle biology overlap in many ways, both with pro- and antiviral outcomes.

Surface Modification of Outer Membrane Vesicles with Glycosylphosphatidylinositol-Anchored Proteins: Generating Pro/Eukaryote Chimera Constructs.

Extracellular vesicles produced by different types of cells have recently attracted great attention, not only for their role in physiology and pathology, but also because of the emerging applications in gene therapy, vaccine production and diagnostics. Less well known than their eukaryotic counterpart, also bacteria produce extracellular vesicles, in the case of the Gram-negative the main species is termed outer membrane vesicles (OMVs). In this study, we show for the first time the functional surface modification of OMVs with glycosylphosphatidylinositol (GPI)-anchored protein, exploiting a process variably described as molecular painting or protein engineering in eukaryotic membranes, whereby the lipid part of the GPI anchor inserts in cell membranes.

Growth rules for the repair of Asynchronous Irregular neuronal networks after peripheral lesions.

Several homeostatic mechanisms enable the brain to maintain desired levels of neuronal activity. One of these, homeostatic structural plasticity, has been reported to restore activity in networks disrupted by peripheral lesions by altering their neuronal connectivity. While multiple lesion experiments have studied the changes in neurite morphology that underlie modifications of synapses in these networks, the underlying mechanisms that drive these changes are yet to be explained.

The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia.

Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV) interneurons in schizophrenia, their functional consequences remain elusive. Since PV interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV interneurons is still unclear.

Biophysical Psychiatry-How Computational Neuroscience Can Help to Understand the Complex Mechanisms of Mental Disorders.

The brain is the most complex of human organs, and the pathophysiology underlying abnormal brain function in psychiatric disorders is largely unknown. Despite the rapid development of diagnostic tools and treatments in most areas of medicine, our understanding of mental disorders and their treatment has made limited progress during the last decades. While recent advances in genetics and neuroscience have a large potential, the complexity and multidimensionality of the brain processes hinder the discovery of disease mechanisms that would link genetic findings to clinical symptoms and behavior.

Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations.

Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters.

Sustainable computational science: the ReScience initiative.

Computer science offers a large set of tools for prototyping, writing, running, testing, validating, sharing and reproducing results; however, computational science lags behind. In the best case, authors may provide their source code as a compressed archive and they may feel confident their research is reproducible. But this is not exactly true.

Real-time analysis of protein and protein mixture interaction with lipid bilayers.

Artificial lipid bilayers in the form of planar supported or vesicular bilayers are commonly used as models for studying interaction of biological membranes with different substances such as proteins and small molecule pharmaceutical compounds. Lipid membranes are typically regarded as inert and passive scaffolds for membrane proteins, but both non-specific and specific interactions between biomolecules and lipid membranes are indeed ubiquitous; dynamic exchange of proteins from the environment at the membrane interface can strongly influence the function of biological membranes. Such exchanges would either be of a superficial (peripheral) or integrative (penetrating) nature.

A stepwise neuron model fitting procedure designed for recordings with high spatial resolution: Application to layer 5 pyramidal cells.

Background: Recent progress in electrophysiological and optical methods for neuronal recordings provides vast amounts of high-resolution data. In parallel, the development of computer technology has allowed simulation of ever-larger neuronal circuits. A challenge in taking advantage of these developments is the construction of single-cell and network models in a way that faithfully reproduces neuronal biophysics with subcellular level of details while keeping the simulation costs at an acceptable level.

Integrated Method for Purification and Single-Particle Characterization of Lentiviral Vector Systems by Size Exclusion Chromatography and Tunable Resistive Pulse Sensing.

Elements derived from lentiviral particles such as viral vectors or virus-like particles are commonly used for biotechnological and biomedical applications, for example in mammalian protein expression, gene delivery or therapy, and vaccine development. Preparations of high purity are necessary in most cases, especially for clinical applications. For purification, a wide range of methods are available, from density gradient centrifugation to affinity chromatography.

Multifactorial Modeling of Impairment of Evoked Gamma Range Oscillations in Schizophrenia.

Despite a significant increase in efforts to identify biomarkers and endophenotypic measures of psychiatric illnesses, only a very limited amount of computational models of these markers and measures has been implemented so far. Moreover, existing computational models dealing with biomarkers typically only examine one possible mechanism in isolation, disregarding the possibility that other combinations of model parameters might produce the same network behavior (what has been termed "multifactoriality"). In this study we describe a step toward a computational instantiation of an endophenotypic finding for schizophrenia, namely the impairment of evoked auditory gamma and beta oscillations in schizophrenia.

Biomedical applications of glycosylphosphatidylinositol-anchored proteins.

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) use a unique posttranslational modification to link proteins to lipid bilayer membranes. The anchoring structure consists of both a lipid and carbohydrate portion and is highly conserved in eukaryotic organisms regarding its basic characteristics, yet highly variable in its molecular details. The strong membrane targeting property has made the anchors an interesting tool for biotechnological modification of lipid membrane-covered entities from cells through extracellular vesicles to enveloped virus particles.

Immune Protection of Retroviral Vectors Upon Molecular Painting with the Complement Regulatory Protein CD59.

Glycosylphosphatidylinositol anchoring is a type of post-translational modification that allows proteins to be presented on the exterior side of the cell membrane. Purified glycosylphosphatidylinositol-anchored protein can spontaneously re-insert into lipid bilayer membranes in a process termed Molecular Painting. Here, we demonstrate the possibility of inserting purified, recombinant CD59 into virus particles produced from a murine retroviral producer cell line.

Quantitative real-time single particle analysis of virions.

Providing information about single virus particles has for a long time been mainly the domain of electron microscopy. More recently, technologies have been developed-or adapted from other fields, such as nanotechnology-to allow for the real-time quantification of physical virion particles, while supplying additional information such as particle diameter concomitantly. These technologies have progressed to the stage of commercialization increasing the speed of viral titer measurements from hours to minutes, thus providing a significant advantage for many aspects of virology research and biotechnology applications.