scholarly journals Development, Modeling, Fabrication, and Characterization of a Magnetic, Micro-Spring-Suspended System for the Safe Electrical Interconnection of Neural Implants

Micromachines ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 424 ◽  
Author(s):  
Katharina Hoch ◽  
Frederick Pothof ◽  
Felix Becker ◽  
Oliver Paul ◽  
Patrick Ruther

The development of innovative tools for neuroscientific research is based on in vivo tests typically applied to small animals. Most often, the interfacing of neural probes relies on commercially available connector systems which are difficult to handle during connection, particularly when freely behaving animals are involved. Furthermore, the connectors often exert high mechanical forces during plugging and unplugging, potentially damaging the fragile bone structure. In order to facilitate connector usage and increase the safety of laboratory animals, we developed a new magnetic connector system circumventing the drawbacks of existing tools. The connector system uses multiple magnet pairs and spring-suspended electrical contact pads realized using micro-electromechanical systems (MEMS) technologies. While the contact pad suspension increases the system tolerance in view of geometrical variations, we achieved a reliable self-alignment of the connector parts at ±50 µm provided by the specifically oriented magnet pairs and without the need of alignment pins. While connection forces are negligible, we can adjust the forces during connector release by modifying the magnet distance. With the connector test structures developed here, we achieved an electrical connection yield of 100%. Based on these findings, we expect that in vivo experiments with freely behaving animals will be facilitated with improved animal safety.

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 70
Author(s):  
Lourdes Mateos-Hernández ◽  
Natália Pipová ◽  
Eléonore Allain ◽  
Céline Henry ◽  
Clotilde Rouxel ◽  
...  

Neuropeptides are small signaling molecules expressed in the tick central nervous system, i.e., the synganglion. The neuronal-like Ixodes scapularis embryonic cell line, ISE6, is an effective tool frequently used for examining tick–pathogen interactions. We detected 37 neuropeptide transcripts in the I. scapularis ISE6 cell line using in silico methods, and six of these neuropeptide genes were used for experimental validation. Among these six neuropeptide genes, the tachykinin-related peptide (TRP) of ISE6 cells varied in transcript expression depending on the infection strain of the tick-borne pathogen, Anaplasma phagocytophilum. The immunocytochemistry of TRP revealed cytoplasmic expression in a prominent ISE6 cell subpopulation. The presence of TRP was also confirmed in A. phagocytophilum-infected ISE6 cells. The in situ hybridization and immunohistochemistry of TRP of I. scapularis synganglion revealed expression in distinct neuronal cells. In addition, TRP immunoreaction was detected in axons exiting the synganglion via peripheral nerves as well as in hemal nerve-associated lateral segmental organs. The characterization of a complete Ixodes neuropeptidome in ISE6 cells may serve as an effective in vitro tool to study how tick-borne pathogens interact with synganglion components that are vital to tick physiology. Therefore, our current study is a potential stepping stone for in vivo experiments to further examine the neuronal basis of tick–pathogen interactions.


2018 ◽  
Vol 11 (4) ◽  
pp. 132 ◽  
Author(s):  
Tais Basaco ◽  
Stefanie Pektor ◽  
Josue Bermudez ◽  
Niurka Meneses ◽  
Manfred Heller ◽  
...  

Girentuximab (cG250) targets carbonic anhydrase IX (CAIX), a protein which is expressed on the surface of most renal cancer cells (RCCs). cG250 labeled with 177Lu has been used in clinical trials for radioimmunotherapy (RIT) of RCCs. In this work, an extensive characterization of the immunoconjugates allowed optimization of the labeling conditions with 177Lu while maintaining immunoreactivity of cG250, which was then investigated in in vitro and in vivo experiments. cG250 was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA(SCN)) by using incubation times between 30 and 90 min and characterized by mass spectrometry. Immunoconjugates with five to ten DOTA(SCN) molecules per cG250 molecule were obtained. Conjugates with ratios less than six DOTA(SCN)/cG250 had higher in vitro antigen affinity, both pre- and postlabeling with 177Lu. Radiochemical stability increased, in the presence of sodium ascorbate, which prevents radiolysis. The immunoreactivity of the radiolabeled cG250 tested by specific binding to SK-RC-52 cells decreased when the DOTA content per conjugate increased. The in vivo tumor uptake was < 10% ID/g and independent of the total amount of protein in the range between 5 and 100 µg cG250 per animal. Low tumor uptake was found to be due to significant necrotic areas and heterogeneous CAIX expression. In addition, low vascularity indicated relatively poor accessibility of the CAIX target.


2018 ◽  
Vol 32 (01) ◽  
pp. 1750274 ◽  
Author(s):  
Ying-Mei Qin ◽  
Cong Men ◽  
Jia Zhao ◽  
Chun-Xiao Han ◽  
Yan-Qiu Che

We focus on the role of heterogeneity on the propagation of firing patterns in feedforward network (FFN). Effects of heterogeneities both in parameters of neuronal excitability and synaptic delays are investigated systematically. Neuronal heterogeneity is found to modulate firing rates and spiking regularity by changing the excitability of the network. Synaptic delays are strongly related with desynchronized and synchronized firing patterns of the FFN, which indicate that synaptic delays may play a significant role in bridging rate coding and temporal coding. Furthermore, quasi-coherence resonance (quasi-CR) phenomenon is observed in the parameter domain of connection probability and delay-heterogeneity. All these phenomena above enable a detailed characterization of neuronal heterogeneity in FFN, which may play an indispensable role in reproducing the important properties of in vivo experiments.


2019 ◽  
Vol 27 (2) ◽  
pp. 245-257 ◽  
Author(s):  
Vyacheslav A. Lipatov ◽  
Aleksey A. Kryukov ◽  
Dmitry A. Severinov ◽  
Araik R. Saakyan

History of experiments on animals began since the time of the anatomist Andreas Vesalius (XVII century) when experiments on animals (vivisection, from Latin vivus, meaning «alive» and sectio, meaning «cutting», literally «cutting the living tissue») were conducted without anesthesia and were extremely cruel. Nowadays use of laboratory animals considerably differs from that in the time of the first experiments and is regulated by certain legal enactments. The aim of the second part of our work is analysis of legal aspects of using animals in in vivo experiments, in particular, provision of them with adequate anesthesiological support. Normative acts regulating principles of work with laboratory animals in different stages of an experiment are considered: animal care, inclusion into experiment, implementation of experiment, withdrawal of animals from the experiment and determination of animals’ fate after the experiment. International and Russian regulatory framework on this issue, in particular, such documents as European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (March 18, 1986, Strasburg), Directive 2010/63/EU on Protection of Animals Used for Scientific Purposes, etc., are considered. Conclusion. At present there exists a sufficient amount of normative enactments regulating implementation of in vivo experimental research. However, most of them require further finalization taking into account recent innovations in medical science and technology. The problem of control of execution of the normative enactments which are in most cases advisory rather than mandatory, remains actual.


2003 ◽  
Vol 77 (20) ◽  
pp. 11268-11273 ◽  
Author(s):  
Nikolai Klymiuk ◽  
Mathias Müller ◽  
Gottfried Brem ◽  
Bernhard Aigner

ABSTRACT Endogenous retrovirus (ERV) sequences have been found in all mammals. In vitro and in vivo experiments revealed ERV activation and cross-species infection in several species. Sheep (Ovis aries) are used for various biotechnological purposes; however, they have not yet been comprehensively screened for ERV sequences. Therefore, the aim of the study was to classify the ERV sequences in the ovine genome (OERV) by analyzing the retroviral pro-pol sequences. Three OERV β families and nine OERV γ families were revealed. Novel open reading frames (ORF) in the amplified proviral fragment were found in one OERV β family and two OERV γ families. Hybrid OERV produced by putative recombination events were not detected. Quantitative analysis of the OERV sequences in the ovine genome revealed no relevant variations in the endogenous retroviral loads of different breeds. Expression analysis of different tissues from fetal and pregnant sheep detected mRNA from both gammaretrovirus families, showing ORF fragments. Thus, the release of retroviruses from sheep cells cannot be excluded.


Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 443 ◽  
Author(s):  
Sumbal Iqbal ◽  
Fawad Ali Shah ◽  
Komal Naeem ◽  
Humaira Nadeem ◽  
Sadia Sarwar ◽  
...  

Oxidative stress-mediated neuroinflammatory events are the hallmark of neurodegenerative diseases. The current study aimed to synthesize a series of novel succinamide derivatives and to further investigate the neuroprotective potential of these compounds against scopolamine-induced neuronal injury by in silico, morphological, and biochemical approaches. The characterization of all the succinamide derivatives was carried out spectroscopically via proton NMR (1H-NMR), FTIR and elemental analysis. Further in vivo experiments showed that scopolamine induced neuronal injury, characterized by downregulated glutathione (GSH), glutathione S-transferase (GST), catalase, and upregulated lipid peroxidation (LPO). Moreover, scopolamine increased the expression of inflammatory mediators such as cyclooxygenase2 (COX2), nuclear factor kappa B (NF-kB), tumor necrosis factor (TNF-α), further associated with cognitive impairment. On the other hand, treatment with succinamide derivatives ameliorated the biochemical and immunohistochemical alterations induced by scopolamine, further supported by the results obtained from molecular docking and binding affinities.


2011 ◽  
Vol 10 ◽  
pp. 896-899 ◽  
Author(s):  
C. Merla ◽  
A. Paffi ◽  
A. D'Attis ◽  
R. Pinto ◽  
M. Liberti ◽  
...  

2019 ◽  
Vol 77 (3) ◽  
Author(s):  
Zhou Zhou ◽  
Na Liu ◽  
Yingzi Wang ◽  
Arthur Wirekoh Emmanuel ◽  
Xiaoxing You ◽  
...  

ABSTRACTObjectiveThis study is to investigate the functions of newly discovered genes in Chlamydia muridarum (C. muridarum) strains with single gene differences.MethodsUsing whole genome sequencing and plaque formation assays, C. muridarum parental and passaging strains were established, and the isogenic clones expressing certain genotypes were isolated. Strains with single gene differences were obtained. Based on prediction, the valuable strains with single gene differences of tc0412, tc0668 or tc0237 were subjected to the in vitro and in vivo experiments for biological characterization and virulence analysis.ResultsInsertional -472840T mutation of the tc0412 gene (T28T/B3 type) matching with the nonmutant tc0668 gene and tc0237 gene with point mutations G797659T (Q117E) might slow the growth of Chlamydia due to the lack of a plasmid. The nonmutant tc0668 in the strain might induce a high incidence of hydrosalpinx in mice, while tc0668 with a G797659T point mutation was significantly attenuated. Compared with the nonmutant tc0237, the strains containing mutant tc0237 were characterized by reduced centrifugation dependence during infection.ConclusionThe identification and characterization of these genes might contribute to the comprehensive understanding of the pathogenic mechanism of Chlamydia.


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