scholarly journals Effects of Pulsed Electric Fields on Yeast with Prions and the Structure of Amyloid Fibrils

2021 ◽  
Vol 11 (6) ◽  
pp. 2684
Author(s):  
Justina Jurgelevičiūtė ◽  
Nedas Bičkovas ◽  
Andrius Sakalauskas ◽  
Vitalij Novickij ◽  
Vytautas Smirnovas ◽  
...  

Prions are misfolded, self-replicating, and transmissible proteins capable of causing different conditions that affect the brain and nervous system in humans and animals. Yeasts are the perfect model to study prion formation, dissemination, and the structure of protein aggregates. Yeast prions are related to stress resistance, cell fitness, and viability. Applying a pulsed electric field (PEF) as a factor capable of disintegrating the amyloid aggregates arises from the fact that the amyloid aggregates form via noncovalent bonds and stabilize via electrostatic interactions. In this research, we applied 2–26 kV/cm PEF delivered in sequences of 5 pulses of 1 ms duration to the Saccharomyces cerevisiae cell without prions and containing strong and weak variants of the [PSI+] prion (prion form of Sup35 translation termination factor). We determined that prions significantly increase cell survivability and resistance to PEF treatment. The application of PEF to the purified Sup35NM fibrils showed that the electric field causes significant reductions in the length of fibrils and the full disintegration of fibrils to Sup35 oligomers can be achieved in higher fields.

2016 ◽  
Vol 18 (48) ◽  
pp. 33310-33319 ◽  
Author(s):  
Winarto Winarto ◽  
Daisuke Takaiwa ◽  
Eiji Yamamoto ◽  
Kenji Yasuoka

Under an electric field, water prefers to fill CNTs over ethanol, and electrostatic interactions within the ordered structure of the water molecules determine the separation effects.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Serena Fiocchi ◽  
Michela Longhi ◽  
Paolo Ravazzani ◽  
Yiftach Roth ◽  
Abraham Zangen ◽  
...  

In the last few years, deep transcranial magnetic stimulation (dTMS) has been used for the treatment of depressive disorders, which affect a broad category of people, from adolescents to aging people. To facilitate its clinical application, particular shapes of coils, including the so-called Hesed coils, were designed. Given their increasing demand and the lack of studies which accurately characterize their use, this paper aims to provide a picture of the distribution of the induced electric field in four realistic human models of different ages and gender. In detail, the electric field distributions were calculated by using numerical techniques in the brain structures potentially involved in the progression of the disease and were quantified in terms of both amplitude levels and focusing power of the distribution. The results highlight how the chosen Hesed coil (H7 coil) is able to induce the maxima levels ofEmainly in the prefrontal cortex, particularly for the younger model. Moreover, growing levels of induced electric fields with age were found by going in deep in the brain, as well as a major capability to penetrate in the deepest brain structures with an electric field higher than 50%, 70%, and 90% of the peak found in the cortex.


2020 ◽  
Author(s):  
Yufan Wu ◽  
Stephen Fried ◽  
Steven Boxer

<div><p>Electrostatic interactions play a pivotal role in enzymatic catalysis and are increasingly modeled explicitly in computational enzyme design; nevertheless, they are challenging to measure experimentally. Using vibrational Stark effect (VSE) spectroscopy, we have measured electric fields inside the active site of the enzyme ketosteroid isomerase (KSI). These studies have shown that these fields can be unusually large, but it has been unclear to what extent they specifically stabilize the transition state (TS) relative to a ground state (GS). In the following, we use crystallography and computational modeling to show that KSI’s intrinsic electric field is nearly perfectly oriented to stabilize the geometry of its reaction’s TS. Moreover, we find that this electric field adjusts the orientation of its substrate in the ground state so that the substrate needs to only undergo minimal structural changes upon activation to its TS. This work provides evidence that the active site electric field in KSI is preorganized to facilitate catalysis and provides a template for how electrostatic preorganization can be measured in enzymatic systems. <br></p></div>


2019 ◽  
Author(s):  
Florian H. Kasten ◽  
Katharina Duecker ◽  
Marike C. Maack ◽  
Arnd Meiser ◽  
Christoph S. Herrmann

AbstractUnderstanding variability of transcranial electrical stimulation (tES) effects is one of the major challenges in the brain stimulation community. Promising candidates to explain this variability are individual anatomy and the resulting differences of electric fields inside the brain. We integrated individual simulations of electric fields during tES with source-localization to predict variability of transcranial alternating current stimulation (tACS) aftereffects on α-oscillations. In two experiments, participants received 20 minutes of either α-tACS (1 mA) or sham stimulation. Magnetoencephalogram was recorded for 10 minutes before and after stimulation. tACS caused a larger power increase in the α-band as compared to sham. The variability of this effect was significantly predicted by measures derived from individual electric field modelling. Our results directly link electric field variability to variability of tACS outcomes, stressing the importance of individualizing stimulation protocols and providing a novel approach to analyze tACS effects in terms of dose-response relationships.


2020 ◽  
Vol 91 (8) ◽  
pp. e6.3-e7
Author(s):  
Nir Grossman

Nir is a Lecturer (Assistant Professor) at Imperial College London and a founding fellow of the UK Dementia Research Institute (UK-DRI). The long-term goal of his research is to develop neuromodulatory interventions for neurodegenerative diseases by direct modulation of the underlying aberrant network activity. Nir received a BSc in Physics from the Israeli Institute of Technology (Technion), an MSc in Electromagnetic Engineering from the Technical University of Hamburg-Harburg, and a PhD in Neuroscience from Imperial College London. He then completed a postdoc training, as a Wellcome Trust Fellow, at the Massachusetts Institute of Technology (MIT) and Harvard University. Nir was recently awarded the prestige prize for Neuromodulation from the Science magazine for describing how temporal interfering of kHz electric fields can non-invasively stimulate focal neural structures deep in the brain.Electrical brain stimulation is a key technique in research and clinical neuroscience studies, and also is in increasingly widespread use from a therapeutic standpoint. However, to date all methods of electrical stimulation of the brain either require surgery to implant an electrode at a defined site, or involve the application of non-focal electric fields to large fractions of the brain. We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice.


2018 ◽  
Author(s):  
Ilkka Laakso ◽  
Marko Mikkonen ◽  
Soichiro Koyama ◽  
Daisuke Ito ◽  
Tomofumi Yamaguchi ◽  
...  

AbstractTranscranial direct current stimulation (TDCS) can modulate motor cortical excitability. However, its after-effects are highly variable between individuals. Individual cranial and brain anatomy may contribute to this variability by producing varying electric fields in each subject’s brain. Here we show that these fields are related to excitability changes following anodal TDCS of the primary motor cortex (M1). We found in two experiments (N=28 and N=9) that the after-effects of TDCS were proportional to the individual electric field in M1, calculated using MRI-based models. Individuals with the lowest and highest local electric fields in M1 tended to produce opposite changes in excitability. Furthermore, the effect was field-direction dependent and non-linear with stimulation duration or other experimental parameters. The electric field component pointing into the brain was negatively proportional to the excitability changes following 1 mA 20 min TDCS of right M1 (N=28); the effect was opposite after 1 mA 10 min TDCS of left M1 (N=9). Our results demonstrate that a large part of variability in the after-effects of motor cortical TDCS is due to inter-individual differences in the electric fields. We anticipate that individualized electric field dosimetry could be used to control the neuroplastic effects of TDCS, which is increasingly being explored as a treatment for various neuropsychiatric diseases.


2018 ◽  
Author(s):  
Guilherme B. Saturnino ◽  
Oula Puonti ◽  
Jesper D Nielsen ◽  
Daria Antonenko ◽  
Kristoffer Hougaard H Madsen ◽  
...  

Numerical simulation of the electric fields induced by Non-Invasive Brain Stimulation (NIBS), using realistic anatomical head models has gained interest in recent years for understanding the NIBS effects in individual subjects. Although automated tools for generating the head models and performing the electric field simulations have become available, individualized modelling is still not standard practice in NIBS studies. This is likely partly explained by the lack of robustness and usability of the previously available software tools, and partly by the still developing understanding of the link between physiological effects and electric field distributions in the brain. To facilitate individualized modelling in NIBS, we have introduced the SimNIBS (Simulation of NIBS) software package, providing easy-to-use automated tools for electric field modelling. In this article, we give an overview of the modelling pipeline in SimNIBS 2.1, with step-by-step examples of how to run a simulation. Furthermore, we demonstrate a set of scripts for extracting average electric fields for a group of subjects, and finally demonstrate the accuracy of automated placement of standard electrode montages on the head model. SimNIBS 2.1 is freely available at www.simnibs.org.


2019 ◽  
Vol 10 ◽  
pp. 111
Author(s):  
Ryosuke Tomio

Background: The aim of this study is to investigate the effects of length and insulation of the corkscrew electrodes for transcranial motor evoked potential (tMEP) monitoring. Methods: We used the finite element method to visualize the electric field in the brain, which was generated by electrodes of different lengths (4, 7, and 12 mm). Two types of head models were generated: A model that included a subcutaneous fat layer and another without a fat layer. Two insulated needle types of conductive tip (5 and 2 mm) were studied. The stimulation threshold levels of hand tMEP were measured in a clinical setting to compare normal corkscrew and insulated 7-mm depth corkscrew. Results: The electric field in the brain depended on the electrode depths in the no fat layer model. The deeper the electrodes reached, the stronger the electric fields generated. Electrode insulation made a difference in the fat layer models. The threshold level recordings of tMEP revealed that the 7-mm insulated electrodes showed a lower threshold than the normal electrodes by one-side replacement in each patient: 33.6 ± 9.6 mA and 36.3 ± 11.0 mA (n =16, P < 0.001), respectively. The 7-mm insulated electrodes also showed a lower threshold than the normal electrodes when both sides, electrodes were replaced: 34.4 ± 8.6 mA and 37.5 ± 9.2 mA (n =10, P = 0.003), respectively. Conclusions: The electrodes depth reached enough to skull is considered to be efficient. Insulation of the electrodes with a conductive tip is efficient when there is subcutaneous fat layer.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Florian H. Kasten ◽  
Katharina Duecker ◽  
Marike C. Maack ◽  
Arnd Meiser ◽  
Christoph S. Herrmann

AbstractTranscranial electrical stimulation (tES) of the brain can have variable effects, plausibly driven by individual differences in neuroanatomy and resulting differences of the electric fields inside the brain. Here, we integrated individual simulations of electric fields during tES with source localization to predict variability of transcranial alternating current stimulation (tACS) aftereffects on α-oscillations. In two experiments, participants received 20-min of either α-tACS (1 mA) or sham stimulation. Magnetoencephalogram (MEG) was recorded for 10-min before and after stimulation. tACS caused a larger power increase in the α-band compared to sham. The variability of this effect was significantly predicted by measures derived from individual electric field modeling. Our results directly link electric field variability to variability of tACS outcomes, underline the importance of individualizing stimulation protocols, and provide a novel approach to analyze tACS effects in terms of dose-response relationships.


Author(s):  
Yufan Wu ◽  
Stephen Fried ◽  
Steven Boxer

<div><p>Electrostatic interactions play a pivotal role in enzymatic catalysis and are increasingly modeled explicitly in computational enzyme design; nevertheless, they are challenging to measure experimentally. Using vibrational Stark effect (VSE) spectroscopy, we have measured electric fields inside the active site of the enzyme ketosteroid isomerase (KSI). These studies have shown that these fields can be unusually large, but it has been unclear to what extent they specifically stabilize the transition state (TS) relative to a ground state (GS). In the following, we use crystallography and computational modeling to show that KSI’s intrinsic electric field is nearly perfectly oriented to stabilize the geometry of its reaction’s TS. Moreover, we find that this electric field adjusts the orientation of its substrate in the ground state so that the substrate needs to only undergo minimal structural changes upon activation to its TS. This work provides evidence that the active site electric field in KSI is preorganized to facilitate catalysis and provides a template for how electrostatic preorganization can be measured in enzymatic systems. <br></p></div>


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