Cell adhesion promotion strategies for signal transduction enhancement in microelectrode array in vitro electrophysiology: An introductory overview and critical discussion

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Molecular Aberrations in Bone Marrow Stromal Cells in Multiple Myeloma

Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of malignant plasma cells within the bone marrow. Bone marrow mesenchymal stromal cells (BMMSCs) represent a crucial component of MM microenvironment supporting its progression and proliferation. Alterations in BMMSC of MM (MM-BMMSC) have become an important research focus. In this study, we analyzed MM-BMMSC and their modification through interaction with plasma cells in 128 MM patients. MM-BMMSC displayed a senescence-like state that was accompanied by an increase in senescence-associated β-galactosidase activity, a reduced number of colony-forming units, an accumulation of cells in S phase of the cell cycle, and the overexpression of microRNAs (miR-16, miR-223, miR-485-5p, and miR-519d) and p21. MM-BMMSC showed a reduced expression of mitochondrial stress response protein SIRT3 and an increased mitochondrial DNA mass that led to a higher amount of reactive oxygen species compared to healthy donor BMMSC. The interaction between MM cells and MM-BMMSC is a complex mechanism that relies on multiple interacting signaling pathways. Observed aberrations in MM-BMMSC should be confirmed in an in vivo model in order to clarify the importance for the pathogenesis of MM. Eventually, the result of MM therapy could be improved by understanding the interaction between MM cells and MM-BMSCs

The Neurally Controlled Animat: Biological Brains Acting with Simulated Bodies

The brain is perhaps the most advanced and robust computation system known. We are creating a method to study how information is processed and encoded in living cultured neuronal networks by interfacing them to a computer-generated animal, the Neurally-Controlled Animat, within a virtual world. Cortical neurons from rats are dissociated and cultured on a surface containing a grid of electrodes (multi-electrode arrays, or MEAs) capable of both recording and stimulating neural activity. Distributed patterns of neural activity are used to control the behavior of the Animat in a simulated environment. The computer acts as its sensory system providing electrical feedback to the network about the Animat's movement within its environment. Changes in the Animat's behavior due to interaction with its surroundings are studied in concert with the biological processes (e.g., neural plasticity) that produced those changes, to understand how information is processed and encoded within a living neural network. Thus, we have created a hybrid real-time processing engine and control system that consists of living, electronic, and simulated components. Eventually this approach may be applied to controlling robotic devices, or lead to better real-time silicon-based information processing and control algorithms that are fault tolerant and can repair themselves

the si elegans project at the interface of experimental and computational caenorhabditis elegans neurobiology and behavior

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Simultaneous two-photon imaging and photo-stimulation with structured light illumination.

Holographic microscopy is increasingly recognized as a promising tool for the study of the central nervous system. Here we present a "holographic module", a simple optical path that can be combined with commercial scanheads for simultaneous imaging and uncaging with structured two-photon light. The present microscope is coupled to two independently tunable lasers and has two principal configurations: holographic imaging combined with galvo-steered uncaging and holographic uncaging combined with conventional scanning imaging. We applied this flexible system for simultaneous two-photon imaging and photostimulation of neuronal cells with complex light patterns, opening new perspectives for the study of brain function in situ and in vivo

A multielectrode array microchannel platform reveals both transient and slow changes in axonal conduction velocity

Due to their small dimensions, electrophysiology on thin and intricate axonal branches in support of understanding their role in normal and diseased brain function poses experimental challenges. To reduce experimental complexity, we coupled microelectrode arrays (MEAs) to bi-level microchannel devices for the long-term in vitro tracking of axonal morphology and activity with high spatiotemporal resolution. Our model allowed the long-term multisite recording from pure axonal branches in a microscopy-compatible environment. Compartmentalizing the network structure into interconnected subpopulations simplified access to the locations of interest. Electrophysiological data over 95 days in vitro (DIV) showed an age-dependent increase of axonal conduction velocity, which was positively correlated with, but independent of evolving burst activity over time. Conduction velocity remained constant at chemically increased network activity levels. In contrast, low frequency (1 Hz, 180 repetitions) electrical stimulation of axons or network subpopulations evoked amplitude-dependent direct (5-35 ms peri-stimulus) and polysynaptic (35-1,000 ms peri-stimulus) activity with temporarily (250 mV) in microchannels when compared with those reported for unconfined cultures (>800 mV). The experimental paradigm may lead to new insights into stimulation-induced axonal plasticity

CD4+ T Cell Dependent B Cell Recovery and Function After Autologous Hematopoietic Stem Cell Transplantation

Introduction: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) represents a standard treatment regime for multiple myeloma (MM) patients. Common and potentially fatal side effects after auto-HSCT are infections due to a severely compromised immune system with hampered humoral and cellular immunity. This study delineates in depth the quantitative and functional B cell defects and investigates underlying extrinsic or intrinsic drivers. Methods: Peripheral blood of MM patients undergoing high-dose chemotherapy and auto-HSCT (before high-dose chemotherapy and in early reconstitution after HSCT) was studied. Absolute numbers and distribution of B cell subsets were analyzed ex vivo using flow cytometry. Additionally, B cell function was assessed with T cell dependent (TD) and T cell independent (TI) stimulation assays, analyzing proliferation and differentiation of B cells by flow cytometry and numbers of immunoglobulin secreting cells in ELISpots. Results: Quantitative B cell defects including a shift in the B cell subset distribution occurred after auto-HSCT. Functionally, these patients showed an impaired TD as well as TI B cell immune response. Individual functional responses correlated with quantitative alterations of CD19+, CD4+, memory B cells and marginal zone-like B cells. The TD B cell function could be partially restored upon stimulation with CD40L/IL-21, successfully inducing B cell proliferation and differentiation into plasmablasts and immunoglobulin secreting cells. Conclusion: Quantitative and functional B cell defects contribute to the compromised immune defense in MM patients undergoing auto-HSCT. Functional recovery upon TD stimulation and correlation with CD4+ T cell numbers, indicate these as extrinsic drivers of the functional B cell defect. Observed correlations of CD4+, CD19+, memory B and MZ-like B cell numbers with the B cell function suggest that these markers should be tested as potential biomarkers in prospective studies

Web-Based Interfaces for Virtual C. elegans Neuron Model Definition, Network Configuration, Behavioral Experiment Definition and Experiment Results Visualization

The Si elegans platform targets the complete virtualization of the nematode Caenorhabditis elegans, and its environment. This paper presents a suite of unified web-based Graphical User Interfaces (GUIs) as the main user interaction point, and discusses their underlying technologies and methods. The user-friendly features of this tool suite enable users to graphically create neuron and network models, and behavioral experiments, without requiring knowledge of domain-specific computer-science tools. The framework furthermore allows the graphical visualization of all simulation results using a worm locomotion and neural activity viewer. Models, experiment definitions and results can be exported in a machine-readable format, thereby facilitating reproducible and cross-platform execution of in silico C. elegans experiments in other simulation environments. This is made possible by a novel XML-based behavioral experiment definition encoding format, a NeuroML XML-based model generation and network configuration description language, and their associated GUIs. User survey data confirms the platform usability and functionality, and provides insights into future directions for web-based simulation GUIs of C. elegans and other living organisms. The tool suite is available online to the scientific community and its source code has been made available