scholarly journals Carbon-Nanotube-Coated Surface Electrodes for Cortical Recordings In Vivo

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1029
Author(s):  
Katharina Foremny ◽  
Wiebke S. Konerding ◽  
Ailke Behrens ◽  
Peter Baumhoff ◽  
Ulrich P. Froriep ◽  
...  
Keyword(s):  
Silicone Rubber ◽  
Auditory Evoked Potentials ◽  
Metal Contacts ◽  
Neural Recordings ◽  
Novel Approach ◽  
Electrophysiological Recordings ◽  
Effective Contact ◽  
Flexible Surface ◽  
Minimal Contact

Current developments of electrodes for neural recordings address the need of biomedical research and applications for high spatial acuity in electrophysiological recordings. One approach is the usage of novel materials to overcome electrochemical constraints of state-of-the-art metal contacts. Promising materials are carbon nanotubes (CNTs), as they are well suited for neural interfacing. The CNTs increase the effective contact surface area to decrease high impedances while keeping minimal contact diameters. However, to prevent toxic dissolving of CNTs, an appropriate surface coating is required. In this study, we tested flexible surface electrocorticographic (ECoG) electrodes, coated with a CNT-silicone rubber composite. First, we describe the outcome of surface etching, which exposes the contact nanostructure while anchoring the CNTs. Subsequently, the ECoG electrodes were used for acute in vivo recordings of auditory evoked potentials from the guinea pig auditory cortex. Both the impedances and the signal-to-noise ratios of coated contacts were similar to uncoated gold contacts. This novel approach for a safe application of CNTs, embedded in a surface etched silicone rubber, showed promising results but did not lead to improvements during acute recordings.

scholarly journals Biocompatibility Testing of Liquid Metal as an Interconnection Material for Flexible Implant Technology

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3251
Author(s):  
Katharina Foremny ◽  
Steven Nagels ◽  
Michaela Kreienmeyer ◽  
Theodor Doll ◽  
Wim Deferme
Keyword(s):  
Liquid Metal ◽  
Silicone Rubber ◽  
Flexible Electronics ◽  
Liquid Metals ◽  
Toxicity Tests ◽  
Electronic Skin ◽  
Flexible Surface ◽  
Biocompatibility Testing ◽  
Interconnection Material

Galinstan, a liquid metal at room temperature, is a promising material for use in flexible electronics. Since it has been successfully integrated in devices for external use, e.g., as stretchable electronic skin in tactile sensation, the possibility of using galinstan for flexible implant technology comes to mind. Usage of liquid metals in a flexible implant would reduce the risk of broken conductive pathways in the implants and therefore reduce the possibility of implant failure. However, the biocompatibility of the liquid metal under study, i.e., galinstan, has not been proven in state-of-the-art literature. Therefore, in this paper, a material combination of galinstan and silicone rubber is under investigation regarding the success of sterilization methods and to establish biocompatibility testing for an in vivo application. First cell biocompatibility tests (WST-1 assays) and cell toxicity tests (LDH assays) show promising results regarding biocompatibility. This work paves the way towards the successful integration of stretchable devices using liquid metals embedded in a silicone rubber encapsulant for flexible surface electro-cortical grid arrays and other flexible implants.

Intraoperative localization of spatially and spectrally distinct resting-state networks in Parkinson’s disease

2020 ◽  
Vol 132 (4) ◽  
pp. 1234-1242 ◽  
Author(s):  
Paolo Belardinelli ◽  
Ramin Azodi-Avval ◽  
Erick Ortiz ◽  
Georgios Naros ◽  
Florian Grimm ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Network Effects ◽  
Brain Activity ◽  
Dynamic Imaging ◽  
Oscillatory Activity ◽  
Network Information ◽  
Novel Approach ◽  
Electrophysiological Recordings ◽  
Intraoperative Localization

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for symptomatic Parkinson’s disease (PD); the clinical benefit may not only mirror modulation of local STN activity but also reflect consecutive network effects on cortical oscillatory activity. Moreover, STN-DBS selectively suppresses spatially and spectrally distinct patterns of synchronous oscillatory activity within cortical-subcortical loops. These STN-cortical circuits have been described in PD patients using magnetoencephalography after surgery. This network information, however, is currently not available during surgery to inform the implantation strategy.The authors recorded spontaneous brain activity in 3 awake patients with PD (mean age 67 ± 14 years; mean disease duration 13 ± 7 years) during implantation of DBS electrodes into the STN after overnight withdrawal of dopaminergic medication. Intraoperative propofol was discontinued at least 30 minutes prior to the electrophysiological recordings. The authors used a novel approach for performing simultaneous recordings of STN local field potentials (LFPs) and multichannel electroencephalography (EEG) at rest. Coherent oscillations between LFP and EEG sensors were computed, and subsequent dynamic imaging of coherent sources was performed.The authors identified coherent activity in the upper beta range (21–35 Hz) between the STN and the ipsilateral mesial (pre)motor area. Coherence in the theta range (4–6 Hz) was detected in the ipsilateral prefrontal area.These findings demonstrate the feasibility of detecting frequency-specific and spatially distinct synchronization between the STN and cortex during DBS surgery. Mapping the STN with this technique may disentangle different functional loops relevant for refined targeting during DBS implantation.

scholarly journals Marker for the pre-clinical development of bone substitute materials

2017 ◽  
Vol 3 (2) ◽  
pp. 711-715
Author(s):  
Michael de Wild ◽  
Simon Zimmermann ◽  
Marcel Obrecht ◽  
Michel Dard
Keyword(s):  
Bone Graft ◽  
Mechanical Stability ◽  
Clinical Performance ◽  
Ex Vivo ◽  
Region Of Interest ◽  
Defect Site ◽  
Novel Approach ◽  
Bone Substitute Materials ◽  
Clinical Experiments

AbstractThin mechanically stable Ti-cages have been developed for the in-vivo application as X-ray and histology markers for the optimized evaluation of pre-clinical performance of bone graft materials. A metallic frame defines the region of interest during histological investigations and supports the identification of the defect site. This standardization of the procedure enhances the quality of pre-clinical experiments. Different models of thin metallic frameworks were designed and produced out of titanium by additive manufacturing (Selective Laser Melting). The productibility, the mechanical stability, the handling and suitability of several frame geometries were tested during surgery in artificial and in ex-vivo bone before a series of cages was preclinically investigated in the female Göttingen minipigs model. With our novel approach, a flexible process was established that can be adapted to the requirements of any specific animal model and bone graft testing.

scholarly journals Artificial Tumor Microenvironments in Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1629
Author(s):  
Colin H. Quinn ◽  
Andee M. Beierle ◽  
Elizabeth A. Beierle
Keyword(s):  
Extracellular Matrix ◽  
Three Dimensional ◽  
Therapeutic Interventions ◽  
3D Bioprinting ◽  
Culture Studies ◽  
In Vivo Models ◽  
Novel Treatments ◽  
Tumor Microenvironments ◽  
Novel Approach

In the quest to advance neuroblastoma therapeutics, there is a need to have a deeper understanding of the tumor microenvironment (TME). From extracellular matrix proteins to tumor associated macrophages, the TME is a robust and diverse network functioning in symbiosis with the solid tumor. Herein, we review the major components of the TME including the extracellular matrix, cytokines, immune cells, and vasculature that support a more aggressive neuroblastoma phenotype and encumber current therapeutic interventions. Contemporary treatments for neuroblastoma are the result of traditional two-dimensional culture studies and in vivo models that have been translated to clinical trials. These pre-clinical studies are costly, time consuming, and neglect the study of cofounding factors such as the contributions of the TME. Three-dimensional (3D) bioprinting has become a novel approach to studying adult cancers and is just now incorporating portions of the TME and advancing to study pediatric solid. We review the methods of 3D bioprinting, how researchers have included TME pieces into the prints, and highlight present studies using neuroblastoma. Ultimately, incorporating the elements of the TME that affect neuroblastoma responses to therapy will improve the development of innovative and novel treatments. The use of 3D bioprinting to achieve this aim will prove useful in developing optimal therapies for children with neuroblastoma.

scholarly journals HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Dan Song ◽  
Ming Guo ◽  
Shuai Xu ◽  
Xiaotian Song ◽  
Bin Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intellectual Development ◽  
Molecular Mechanisms ◽  
Hsp90 Inhibitor ◽  
Pseudouridine Synthase ◽  
Novel Approach ◽  
Cell Metastasis ◽  
Underlying Mechanisms

Abstract Background Pseudouridine synthase (PUS) 7 is a member of the PUS family that catalyses pseudouridine formation. It has been shown to be involved in intellectual development and haematological malignancies. Nevertheless, the role and the underlying molecular mechanisms of PUS7 in solid tumours, such as colorectal cancer (CRC), remain unexplored. This study elucidated, for the first time, the role of PUS7 in CRC cell metastasis and the underlying mechanisms. Methods We conducted immunohistochemistry, qPCR, and western blotting to quantify the expression of PUS7 in CRC tissues as well as cell lines. Besides, diverse in vivo and in vitro functional tests were employed to establish the function of PUS7 in CRC. RNA-seq and proteome profiling analysis were also applied to identify the targets of PUS7. PUS7-interacting proteins were further uncovered using immunoprecipitation and mass spectrometry. Results Overexpression of PUS7 was observed in CRC tissues and was linked to advanced clinical stages and shorter overall survival. PUS7 silencing effectively repressed CRC cell metastasis, while its upregulation promoted metastasis, independently of the PUS7 catalytic activity. LASP1 was identified as a downstream effector of PUS7. Forced LASP1 expression abolished the metastasis suppression triggered by PUS7 silencing. Furthermore, HSP90 was identified as a client protein of PUS7, associated with the increased PUS7 abundance in CRC. NMS-E973, a specific HSP90 inhibitor, also showed higher anti-metastatic activity when combined with PUS7 repression. Importantly, in line with these results, in human CRC tissues, the expression of PUS7 was positively linked to the expression of HSP90 and LASP1, and patients co-expressing HSP90/PUS7/LASP1 showed a worse prognosis. Conclusions The HSP90-dependent PUS7 upregulation promotes CRC cell metastasis via the regulation of LASP1. Thus, targeting the HSP90/PUS7/LASP1 axis may be a novel approach for the treatment of CRC.

scholarly journals Three-dimensional in situ morphometrics of Mycobacterium tuberculosis infection within lesions by optical mesoscopy and novel acid-fast staining

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Robert J. Francis ◽  
Gillian Robb ◽  
Lee McCann ◽  
Bhagwati Khatri ◽  
James Keeble ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Three Dimensional ◽  
Large Field ◽  
Staining Procedure ◽  
3D Analysis ◽  
Mycobacterium Tuberculosis Infection ◽  
In Vivo Models ◽  
Novel Approach

AbstractTuberculosis (TB) preclinical testing relies on in vivo models including the mouse aerosol challenge model. The only method of determining colony morphometrics of TB infection in a tissue in situ is two-dimensional (2D) histopathology. 2D measurements consider heterogeneity within a single observable section but not above and below, which could contain critical information. Here we describe a novel approach, using optical clearing and a novel staining procedure with confocal microscopy and mesoscopy, for three-dimensional (3D) measurement of TB infection within lesions at sub-cellular resolution over a large field of view. We show TB morphometrics can be determined within lesion pathology, and differences in infection with different strains of Mycobacterium tuberculosis. Mesoscopy combined with the novel CUBIC Acid-Fast (CAF) staining procedure enables a quantitative approach to measure TB infection and allows 3D analysis of infection, providing a framework which could be used in the analysis of TB infection in situ.

scholarly journals Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs

2021 ◽  
Vol 7 (9) ◽  
pp. eabb0737
Author(s):  
Zhengnan Yang ◽  
Wei Wang ◽  
Linjie Zhao ◽  
Xin Wang ◽  
Ryan C. Gimple ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Phenotype ◽  
Ovarian Cancers ◽  
Novel Approach

Ovarian cancer represents a highly lethal disease that poses a substantial burden for females, with four main molecular subtypes carrying distinct clinical outcomes. Here, we demonstrated that plasma cells, a subset of antibody-producing B cells, were enriched in the mesenchymal subtype of high-grade serous ovarian cancers (HGSCs). Plasma cell abundance correlated with the density of mesenchymal cells in clinical specimens of HGSCs. Coculture of nonmesenchymal ovarian cancer cells and plasma cells induced a mesenchymal phenotype of tumor cells in vitro and in vivo. Phenotypic switch was mediated by the transfer of plasma cell–derived exosomes containing miR-330-3p into nonmesenchymal ovarian cancer cells. Exosome-derived miR-330-3p increased expression of junctional adhesion molecule B in a noncanonical fashion. Depletion of plasma cells by bortezomib reversed the mesenchymal characteristics of ovarian cancer and inhibited in vivo tumor growth. Collectively, our work suggests targeting plasma cells may be a novel approach for ovarian cancer therapy.

scholarly journals THER-05. GENETICALLY STABLE POLIOVIRUS VECTOR CARRYING H3.3K27M ANTIGEN FOR TREATMENT OF DIFFUSE MIDLINE GLIOMA BY INTRAMUSCULAR INJECTION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii472-iii472
Author(s):  
Mubeen Mosaheb ◽  
Daniel Landi ◽  
Elena Dobrikova ◽  
Michael Brown ◽  
Yuanfan Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Intramuscular Injection ◽  
Cd8 T Cell ◽  
Cytokine Profiles ◽  
Cell Immunity ◽  
Novel Approach ◽  
Diffuse Midline Glioma

Abstract BACKGROUND H3 K27M-mutant diffuse midline glioma (DMG) is invariably lethal. Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses, in particular, are uniquely tropic for dendritic cells (DC) and potently activate DC, inducing Th1-dominant cytokine profiles, CD8 T cell immunity, and enhanced epitope presentation. Thus, poliovirus is ideally suited for vectored delivery of signature tumor neoantigens, e.g. the H3 K27M feature of DMG. However, poliovirus vector design is inherently limited by genetic instability and the underlying neuropathogenicity of poliovirus. METHODS We created a genetically stable, polio:rhinovirus chimera vector devoid of neuropathogenicity and modified for stable expression of the HLA-A2 restricted H3.3 K27M antigen (RIPO (H3.3)). RESULTS RIPO(H3.3) infects, activates, and induces H3.3K27M antigen presentation in DCs in vitro. Given intramuscularly in vivo, RIPO(H3.3) recruits and activates DCs with Th1-dominant cytokine profiles, efficiently primes H3.3K27M-specific CD8 T cells, induces antigen-specific CD8 T cell migration to the tumor site, delays tumor growth, and enhances survival in murine tumor models. CONCLUSION This novel approach leverages the unique ability of polioviruses to activate DCs while simultaneously introducing the H3.3 K27M antigen. In this way, DCs are activated optimally in situ, while being simultaneously infected to express/present tumor antigen. RIPO(H3.3), given by intramuscular injection, will be evaluated in a clinical trial for children with H3 K27M-mutant diffuse midline glioma.

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