scholarly journals A 3D flexible neural interface based on a microfluidic interconnection cable capable of chemical delivery

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yoo Na Kang ◽  
Namsun Chou ◽  
Jae-Won Jang ◽  
Han Kyoung Choe ◽  
Sohee Kim
Keyword(s):  
Microelectrode Array ◽  
Neurological Diseases ◽  
Three Dimensional ◽  
Critical Issue ◽  
Neural Interface ◽  
Neural Interfaces ◽  
Dimensional Structure ◽  
Microfluidic Channels ◽  
Before And After

AbstractThe demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks. Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain, and it expands the utility of drugs by bypassing the blood–brain barrier (BBB). In addition, uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes, pointing to a critical issue still to be overcome. Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications, it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures, which differ from two-dimensionally fabricated shank-type neural probes. Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality. We fabricated a microfluidic interconnection cable (µFIC) and integrated it with a flexible penetrating microelectrode array (FPMA) that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base. We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection. This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities.

scholarly journals Three-dimensional analysis of the root canal preparation with Reciproc Blue®, WaveOne Gold® and XP EndoShaper®: a new method in vivo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Javier Caviedes-Bucheli ◽  
Nestor Rios-Osorio ◽  
Diana Usme ◽  
Cristian Jimenez ◽  
Adriana Pinzon ◽  
...  
Keyword(s):  
3D Reconstruction ◽  
Root Canal ◽  
Paired Comparison ◽  
Three Dimensional ◽  
New Method ◽  
Root Canal Preparation ◽  
Paired Data ◽  
Before And After ◽  
Student’S T

Abstract Background The purpose of this study was to evaluate the changes in canal volume after root canal preparation in vivo with 3 different single-file techniques (Reciproc-Blue®, WaveOne-Gold® and XP-EndoShaper®), with a new method using CBCT and 3D reconstruction. Methods In this prospective study, thirty human lower premolars from healthy patients were used, in which extraction was indicated for orthodontic reasons. All the teeth used were caries- and restoration-free with complete root development, without signs of periodontal disease or traumatic occlusion, and with only one straight canal (up to 25º curvature). Teeth were randomly divided into three different groups: Reciproc-Blue, WaveOne-Gold and XP-EndoShaper. CBCT scans before root canal preparation were used to create a 3D reconstruction with RHINOCEROS 5.0 software to assess the initial canal volume, and then compared with 3D reconstructions after canal preparation to measure the increase in canal volume. Student’s t test for paired data were used to determine statistically significant differences between the before and after canal volumes. Anova test was used to determine statistically significant differences in the percentage of canal volume increase between the groups and Tukey's post-hoc test were used to paired comparison. Results Reciproc-Blue showed the higher increase in canal volume, followed by WaveOne-Gold and XP-EndoShaper (p = 0.003). XP-EndoShaper did not show a statistically significant increase in canal volume after root canal preparation (p = 0.06). Conclusion With this model, Reciproc-Blue showed higher increase in root canal volume, followed by WaveOne-Gold, while XP-EndoShaper did not significantly increase root canal volume during preparation.

scholarly journals Structure of the Lectin Mannose 6-Phosphate Receptor Homology (MRH) Domain of Glucosidase II, an Enzyme That Regulates Glycoprotein Folding Quality Control in the Endoplasmic Reticulum

2013 ◽  
Vol 288 (23) ◽  
pp. 16460-16475 ◽  
Author(s):  
Linda J. Olson ◽  
Ramiro Orsi ◽  
Solana G. Alculumbre ◽  
Francis C. Peterson ◽  
Ivan D. Stigliano ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Three Dimensional ◽  
Binding Pocket ◽  
Dimensional Structure ◽  
Mannose Residue ◽  
Glucosidase Ii ◽  
Mannose 6 Phosphate ◽  
First Time ◽  
Conserved Residue

Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and the glucose added by UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GIIα subunit and a regulatory GIIβ subunit. GIIβ participates in the endoplasmic reticulum localization of GIIα and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIβ MRH domain by NMR spectroscopy. It adopts a β-barrel fold similar to that of other MRH domains, but its binding pocket is the most shallow known to date as it accommodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIβ but not in other MRHs that influences GII glucose trimming activity.

A Cadaveric and Magnetic Resonance Imaging Investigation of the Salpingopharyngeus

2021 ◽  
pp. 1-11
Author(s):  
Karen Perta ◽  
Eileen Kalmar ◽  
Youkyung Bae
Keyword(s):  
Magnetic Resonance Imaging ◽  
Body Weight ◽  
Magnetic Resonance ◽  
Three Dimensional ◽  
Hierarchical Regression ◽  
Resonance Imaging ◽  
Before And After ◽  
Velopharyngeal Function ◽  
The Relationship

Purpose The aim of the study was to update our information regarding the salpingopharyngeus (SP) muscle using cadaveric and in vivo magnetic resonance imaging (MRI) data. Primary objectives were to (a) observe the presence/absence of the muscle and (b) quantify and describe its dimensions and course. Method SP specimens from 19 cadavers (10 women, nine men) were analyzed. Following head bisection, measurements of SP, including width of the cartilaginous attachment (CW) and width of the superior muscle base (SMW), were taken before and after removal of the overlying mucosa. In addition, SP was analyzed in 15 healthy subjects (eight men, seven women) using high-resolution three-dimensional MRI data. CW and SMW measures were replicated in the paraxial MRI view. Results The presence of the salpingopharyngeal fold and muscle was confirmed bilaterally in all cadaveric and living subjects. Following mucosa removal, mean cadaveric CW and SMW measurements were 5.6 and 3.8 mm, respectively. Mean in vivo CW and SMW were 6.1 and 3.7 mm, respectively. Results from the hierarchical regression analyses revealed that, in both cadaveric and living groups, SMW is dependent on the relationship between age and body weight, after controlling for sex. Conclusions The salpingopharyngeal fold and SP muscle are always present bilaterally and can be quantified at the superior origin using both cadaveric and in vivo three-dimensional MRI data. Though both the superior origin and inferior course of SP are highly variable, the size of the SP muscle is dependent on characteristics known to affect muscle fibers, such as the relationship between age and body weight. Given the consistent and quantifiable presence of the SP muscle, its potential role in velopharyngeal function for speech and swallowing is reconsidered. Supplemental Material https://doi.org/10.23641/asha.14347859

scholarly journals Protein Folding: Search for Basic Physical Models

2003 ◽  
Vol 3 ◽  
pp. 623-635 ◽  
Author(s):  
Ivan Y. Torshin ◽  
Robert W. Harrison
Keyword(s):  
Protein Folding ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Physical Models ◽  
Dimensional Structure ◽  
Computational Techniques ◽  
Linear Sequence ◽  
Physical Forces

How a unique three-dimensional structure is rapidly formed from the linear sequence of a polypeptide is one of the important questions in contemporary science. Apart from biological context ofin vivoprotein folding (which has been studied only for a few proteins), the roles of the fundamental physical forces in thein vitrofolding remain largely unstudied. Despite a degree of success in using descriptions based on statistical and/or thermodynamic approaches, few of the current models explicitly include more basic physical forces (such as electrostatics and Van Der Waals forces). Moreover, the present-day models rarely take into account that the protein folding is, essentially, a rapid process that produces a highly specific architecture. This review considers several physical models that may provide more direct links between sequence and tertiary structure in terms of the physical forces. In particular, elaboration of such simple models is likely to produce extremely effective computational techniques with value for modern genomics.

scholarly journals Computational Protein Stabilization Can Affect Folding Energy Landscapes and Lead to Domain-Swapped Dimers

2021 ◽  
Author(s):  
Klara Markova ◽  
Antonin Kunka ◽  
Klaudia Chmelova ◽  
Martin Havlasek ◽  
Petra Babkova ◽  
...  
Keyword(s):  
Protein Folding ◽  
Protein Design ◽  
Energy Landscape ◽  
Single Point ◽  
Three Dimensional ◽  
Protein Stabilization ◽  
Dimensional Structure ◽  
Evolutionary Analysis ◽  
Folding Energy

<p>The functionality of a protein depends on its unique three-dimensional structure, which is a result of the folding process when the nascent polypeptide follows a funnel-like energy landscape to reach a global energy minimum. Computer-encoded algorithms are increasingly employed to stabilize native proteins for use in research and biotechnology applications. Here, we reveal a unique example where the computational stabilization of a monomeric α/β-hydrolase enzyme (<i>T</i><sub>m</sub> = 73.5°C; Δ<i>T</i><sub>m</sub> > 23°C) affected the protein folding energy landscape. Introduction of eleven single-point stabilizing mutations based on force field calculations and evolutionary analysis yielded catalytically active domain-swapped intermediates trapped in local energy minima. Crystallographic structures revealed that these stabilizing mutations target cryptic hinge regions and newly introduced secondary interfaces, where they make extensive non-covalent interactions between the intertwined misfolded protomers. The existence of domain-swapped dimers in a solution is further confirmed experimentally by data obtained from SAXS and crosslinking mass spectrometry. Unfolding experiments showed that the domain-swapped dimers can be irreversibly converted into native-like monomers, suggesting that the domain-swapping occurs exclusively <i>in vivo</i>. Our findings uncovered hidden protein-folding consequences of computational protein design, which need to be taken into account when applying a rational stabilization to proteins of biological and pharmaceutical interest.</p>

scholarly journals Computational Protein Stabilization Can Affect Folding Energy Landscapes and Lead to Domain-Swapped Dimers

2021 ◽  
Author(s):  
Klara Markova ◽  
Antonin Kunka ◽  
Klaudia Chmelova ◽  
Martin Havlasek ◽  
Petra Babkova ◽  
...  
Keyword(s):  
Protein Folding ◽  
Protein Design ◽  
Energy Landscape ◽  
Single Point ◽  
Three Dimensional ◽  
Protein Stabilization ◽  
Dimensional Structure ◽  
Evolutionary Analysis ◽  
Folding Energy

<p>The functionality of a protein depends on its unique three-dimensional structure, which is a result of the folding process when the nascent polypeptide follows a funnel-like energy landscape to reach a global energy minimum. Computer-encoded algorithms are increasingly employed to stabilize native proteins for use in research and biotechnology applications. Here, we reveal a unique example where the computational stabilization of a monomeric α/β-hydrolase enzyme (<i>T</i><sub>m</sub> = 73.5°C; Δ<i>T</i><sub>m</sub> > 23°C) affected the protein folding energy landscape. Introduction of eleven single-point stabilizing mutations based on force field calculations and evolutionary analysis yielded catalytically active domain-swapped intermediates trapped in local energy minima. Crystallographic structures revealed that these stabilizing mutations target cryptic hinge regions and newly introduced secondary interfaces, where they make extensive non-covalent interactions between the intertwined misfolded protomers. The existence of domain-swapped dimers in a solution is further confirmed experimentally by data obtained from SAXS and crosslinking mass spectrometry. Unfolding experiments showed that the domain-swapped dimers can be irreversibly converted into native-like monomers, suggesting that the domain-swapping occurs exclusively <i>in vivo</i>. Our findings uncovered hidden protein-folding consequences of computational protein design, which need to be taken into account when applying a rational stabilization to proteins of biological and pharmaceutical interest.</p>

scholarly journals Antibodies against Thrombospondin-Related Anonymous Protein Do Not Inhibit Plasmodium Sporozoite Infectivity In Vivo

2000 ◽  
Vol 68 (6) ◽  
pp. 3667-3673 ◽  
Author(s):  
Soren Gantt ◽  
Cathrine Persson ◽  
Keith Rose ◽  
Ashley J. Birkett ◽  
Ruben Abagyan ◽  
...  
Keyword(s):  
Metal Ion ◽  
Competitive Inhibition ◽  
Polyclonal Antibodies ◽  
Three Dimensional ◽  
Calcium Ionophore ◽  
Plasmodium Yoelii ◽  
Gliding Motility ◽  
Vaccine Antigen ◽  
Dimensional Structure

ABSTRACT Thrombospondin-related anonymous protein (TRAP), a candidate malaria vaccine antigen, is required for Plasmodiumsporozoite gliding motility and cell invasion. For the first time, the ability of antibodies against TRAP to inhibit sporozoite infectivity in vivo is evaluated in detail. TRAP contains an A-domain, a well-characterized adhesive motif found in integrins. We modeled here a three-dimensional structure of the TRAP A-domain of Plasmodium yoelii and located regions surrounding the MIDAS (metal ion-dependent adhesion site), the presumed business end of the domain. Mice were immunized with constructs containing these A-domain regions but were not protected from sporozoite challenge. Furthermore, monoclonal and rabbit polyclonal antibodies against the A-domain, the conserved N terminus, and the repeat region of TRAP had no effect on the gliding motility or sporozoite infectivity to mice. TRAP is located in micronemes, secretory organelles of apicomplexan parasites. Accordingly, the antibodies tested here stained cytoplasmic TRAP brightly by immunofluorescence. However, very little TRAP could be detected on the surface of sporozoites. In contrast, a dramatic relocalization of TRAP onto the parasite surface occurred when sporozoites were treated with calcium ionophore. This likely mimics the release of TRAP from micronemes when a sporozoite contacts its target cell in vivo. Contact with hepatoma cells in culture also appeared to induce the release of TRAP onto the surface of sporozoites. If large amounts of TRAP are released in close proximity to its cellular receptor(s), effective competitive inhibition by antibodies may be difficult to achieve.

scholarly journals Role of YidC in folding of polytopic membrane proteins

2004 ◽  
Vol 165 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Shushi Nagamori ◽  
Irina N. Smirnova ◽  
H. Ronald Kaback
Keyword(s):  
Membrane Proteins ◽  
Three Dimensional ◽  
In Vitro Transcription ◽  
Dimensional Structure ◽  
Lipid Phase ◽  
Lactose Permease ◽  
Primary Role ◽  
Protein Insertion

YidC of Echerichia coli, a member of the conserved Alb3/Oxa1/YidC family, is postulated to be important for biogenesis of membrane proteins. Here, we use as a model the lactose permease (LacY), a membrane transport protein with a known three-dimensional structure, to determine whether YidC plays a role in polytopic membrane protein insertion and/or folding. Experiments in vivo and with an in vitro transcription/translation/insertion system demonstrate that YidC is not necessary for insertion per se, but plays an important role in folding of LacY. By using the in vitro system and two monoclonal antibodies directed against conformational epitopes, LacY is shown to bind the antibodies poorly in YidC-depleted membranes. Moreover, LacY also folds improperly in proteoliposomes prepared without YidC. However, when the proteoliposomes are supplemented with purified YidC, LacY folds correctly. The results indicate that YidC plays a primary role in folding of LacY into its final tertiary conformation via an interaction that likely occurs transiently during insertion into the lipid phase of the membrane.

scholarly journals Insights into the molecular basis of sperm–egg recognition in mammals

Reproduction ◽  
2004 ◽  
Vol 127 (4) ◽  
pp. 417-422 ◽  
Author(s):  
Tanya Hoodbhoy ◽  
Jurrien Dean
Keyword(s):  
Zona Pellucida ◽  
Three Dimensional ◽  
Explanatory Models ◽  
Dimensional Structure ◽  
Side Chain ◽  
Egg Recognition ◽  
Three Dimensional Structure ◽  
Sperm Binding ◽  
Single Protein

The zona pellucida surrounding the egg and pre-implantation embryo is required for in vivo fertility and early development. Explanatory models of sperm–egg recognition need to take into account the ability of sperm to bind to ovulated eggs, but not to two-cell embryos. For the last two decades, investigators have sought to identify an individual protein or carbohydrate side chain as the ‘sperm receptor’. However, recent genetic data in mice are more consistent with the three-dimensional structure of the zona pellucida, rather than a single protein (or carbohydrate), determining sperm binding. The mouse and human zonae pellucidae contain three glycoproteins (ZP1, ZP2, ZP3) and, following fertilization, ZP2 is proteolytically cleaved. The replacement of endogenous mouse proteins with human ZP2, ZP3 or both does not alter taxon specificity of sperm binding or prevent fertility. Surprisingly, human ZP2 is not cleaved following fertilization and intact ZP2 correlates with persistent sperm binding to two-cell embryos. Taken together, these data support a model in which the cleavage status of ZP2 modulates the three-dimensional structure of the zona pellucida and determines whether sperm bind (uncleaved) or do not (cleaved).

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