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Open AccessReview
A Review on Ultrasonic Neuromodulation of the Peripheral Nervous System: Enhanced or Suppressed Activities?
Appl. Sci. 2019, 9(8), 1637; https://doi.org/10.3390/app9081637 (registering DOI) -
Abstract
Ultrasonic (US) neuromodulation has emerged as a promising therapeutic means by delivering focused energy deep into the nervous tissue. Low-intensity ultrasound (US) directly activates and/or inhibits neurons in the central nervous system (CNS). US neuromodulation of the peripheral nervous system (PNS) is less [...] Read more.
Ultrasonic (US) neuromodulation has emerged as a promising therapeutic means by delivering focused energy deep into the nervous tissue. Low-intensity ultrasound (US) directly activates and/or inhibits neurons in the central nervous system (CNS). US neuromodulation of the peripheral nervous system (PNS) is less developed and rarely used clinically. The literature on the neuromodulatory effects of US on the PNS is controversial, with some studies documenting enhanced neural activities, some showing suppressed activities, and others reporting mixed effects. US, with different ranges of intensity and strength, is likely to generate distinct physical effects in the stimulated neuronal tissues, which underlies different experimental outcomes in the literature. In this review, we summarize all the major reports that document the effects of US on peripheral nerve endings, axons, and/or somata in the dorsal root ganglion. In particular, we thoroughly discuss the potential impacts of the following key parameters on the study outcomes of PNS neuromodulation by US: frequency, pulse repetition frequency, duty cycle, intensity, metrics for peripheral neural activities, and type of biological preparations used in the studies. Potential mechanisms of peripheral US neuromodulation are summarized to provide a plausible interpretation of the seemly contradictory effects of enhanced and suppressed neural activities of US neuromodulation. Full article
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Open AccessFeature PaperReview
Long Non-Coding RNAs and the Innate Immune Response
Non-Coding RNA 2019, 5(2), 34; https://doi.org/10.3390/ncrna5020034 (registering DOI) -
Abstract
Innate immunity provides the initial defence against infection and it is now clear that long non-coding RNAs (lncRNAs) are important regulators of this response. Following activation of the innate response, we commonly see rapid induction of these lncRNAs and this is often mediated [...] Read more.
Innate immunity provides the initial defence against infection and it is now clear that long non-coding RNAs (lncRNAs) are important regulators of this response. Following activation of the innate response, we commonly see rapid induction of these lncRNAs and this is often mediated via the pro-inflammatory transcription factor, nuclear factor-κB (NF-κB). Knockdown studies have shown that lncRNAs tend to act in trans to regulate the expression of multiple inflammatory mediators and other responses. Mechanistically, many lncRNAs have demonstrated acting through heterogeneous nuclear ribonucleoproteins, complexes that are implicated chromatin re-modelling, transcription process and translation. In addition, these lncRNAs have also been shown to interact with multiple other proteins involved in the regulation of chromatin re-modelling, as well as those proteins involved in intracellular immune signalling, which include NF-κB. In this review, we will describe the evidence that supports this emerging role of lncRNA in the innate immune response. Full article
Open AccessReview
Laser Ablation Inductively Coupled Plasma Spectrometry: Metal Imaging in Experimental and Clinical Wilson Disease
Inorganics 2019, 7(4), 54; https://doi.org/10.3390/inorganics7040054 (registering DOI) -
Abstract
Wilson disease is an inherited disorder caused by mutations in the ATP7B gene resulting in copper metabolism disturbances. As a consequence, copper accumulates in different organs with most common presentation in liver and brain. Chelating agents that nonspecifically chelate copper, and promote its [...] Read more.
Wilson disease is an inherited disorder caused by mutations in the ATP7B gene resulting in copper metabolism disturbances. As a consequence, copper accumulates in different organs with most common presentation in liver and brain. Chelating agents that nonspecifically chelate copper, and promote its urinary excretion, or zinc salts interfering with the absorption of copper from the gastrointestinal tract, are current medications. Also gene therapy, restoring ATP7B gene function or trials with bis-choline tetrathiomolybdate (WTX101) removing excess copper from intracellular hepatic copper stores and increasing biliary copper excretion, is promising in reducing body’s copper content. Therapy efficacy is mostly evaluated by testing for evidence of liver disease and neurological symptoms, hepatic synthetic functions, indices of copper metabolisms, urinary copper excretions, or direct copper measurements. However, several studies conducted in patients or Wilson disease models have shown that not only the absolute concentration of copper, but also its spatial distribution within the diseased tissue is relevant for disease severity and outcome. Here we discuss laser ablation inductively coupled plasma spectrometry imaging as a novel method for accurate determination of trace element concentrations with high diagnostic sensitivity, spatial resolution, specificity, and quantification ability in experimental and clinical Wilson disease specimens. Full article
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Open AccessFeature PaperArticle
Investigating the Molecular Basis of N-Substituted 1-Hydroxy-4-Sulfamoyl-2-Naphthoate Compounds Binding to Mcl1
Processes 2019, 7(4), 224; https://doi.org/10.3390/pr7040224 (registering DOI) -
Abstract
Myeloid cell leukemia-1 (Mcl1) is an anti–apoptotic protein that has gained considerable attention due to its overexpression activity prevents cell death. Therefore, a potential inhibitor that specifically targets Mcl1 with higher binding affinity is necessary. Recently, a series of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoate compounds was [...] Read more.
Myeloid cell leukemia-1 (Mcl1) is an anti–apoptotic protein that has gained considerable attention due to its overexpression activity prevents cell death. Therefore, a potential inhibitor that specifically targets Mcl1 with higher binding affinity is necessary. Recently, a series of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoate compounds was reported that targets Mcl1, but its binding mechanism remains unexplored. Here, we attempted to explore the molecular mechanism of binding to Mcl1 using advanced computational approaches: pharmacophore-based 3D-QSAR, docking, and MD simulation. The selected pharmacophore—NNRRR—yielded a statistically significant 3D-QSAR model containing high confidence scores (R2 = 0.9209, Q2 = 0.8459, and RMSE = 0.3473). The contour maps—comprising hydrogen bond donor, hydrophobic, negative ionic and electron withdrawal effects—from our 3D-QSAR model identified the favorable regions crucial for maximum activity. Furthermore, the external validation of the selected model using enrichment and decoys analysis reveals a high predictive power. Also, the screening capacity of the selected model had scores of 0.94, 0.90, and 8.26 from ROC, AUC, and RIE analysis, respectively. The molecular docking of the highly active compound—C40; 4-(N-benzyl-N-(4-(4-chloro-3,5-dimethylphenoxy) phenyl) sulfamoyl)-1-hydroxy-2-naphthoate—predicted the low-energy conformational pose, and the MD simulation revealed crucial details responsible for the molecular mechanism of binding with Mcl1. Full article
Open AccessReview
The Potential of the Cyclotide Scaffold for Drug Development
Biomedicines 2019, 7(2), 31; https://doi.org/10.3390/biomedicines7020031 (registering DOI) -
Abstract
Cyclotides are a novel class of micro-proteins (≈30–40 residues long) with a unique topology containing a head-to-tail cyclized backbone structure further stabilized by three disulfide bonds that form a cystine knot. This unique molecular framework makes them exceptionally stable to physical, chemical, and [...] Read more.
Cyclotides are a novel class of micro-proteins (≈30–40 residues long) with a unique topology containing a head-to-tail cyclized backbone structure further stabilized by three disulfide bonds that form a cystine knot. This unique molecular framework makes them exceptionally stable to physical, chemical, and biological degradation compared to linear peptides of similar size. The cyclotides are also highly tolerant to sequence variability, aside from the conserved residues forming the cystine knot, and are orally bioavailable and able to cross cellular membranes to modulate intracellular protein–protein interactions (PPIs), both in vitro and in vivo. These unique properties make them ideal scaffolds for many biotechnological applications, including drug discovery. This review provides an overview of the properties of cyclotides and their potential for the development of novel peptide-based therapeutics. The selective disruption of PPIs still remains a very challenging task, as the interacting surfaces are relatively large and flat. The use of the cell-permeable highly constrained polypeptide molecular frameworks, such as the cyclotide scaffold, has shown great promise, as it provides unique pharmacological properties. The use of molecular techniques, such as epitope grafting, and molecular evolution have shown to be highly effective for the selection of bioactive cyclotides. However, despite successes in employing cyclotides to target PPIs, some of the challenges to move them into the clinic still remain. Full article
Open AccessArticle
A Capacitor Voltage Balancing Approach Based on Mapping Strategy for MMC Applications
Electronics 2019, 8(4), 449; https://doi.org/10.3390/electronics8040449 (registering DOI) -
Abstract
This paper proposes a new strategy to achieve balanced capacitor voltages in modular multilevel converters. Among the possible solutions, centralized arm control approaches are often adopted. These methods require a balancing technique based on a sorted list of the sub-modules according to their [...] Read more.
This paper proposes a new strategy to achieve balanced capacitor voltages in modular multilevel converters. Among the possible solutions, centralized arm control approaches are often adopted. These methods require a balancing technique based on a sorted list of the sub-modules according to their capacitor voltages. In order to achieve the aforementioned sorted list, different algorithms have been proposed in literature, such as: Sorting algorithms, max/min approaches, etc. However, the sorting algorithms require a long execution time, while the max/min approaches affect the converter dynamic response during faults. To overcome these issues, a new mapping strategy providing a quasi-sorted list is proposed in this paper. The suggested method is compared in simulation with both the classical bubble sorting algorithm, and the max/min method during both normal and faulty conditions. Moreover, the three methods have been implemented in a Xilinx Zynq-7000 System-on-Chip (SoC) device, in order to analyze the corresponding execution time and the required computational effort. Hardware-in-the-loop results are presented for demonstrating the superior performance of the proposed balancing strategy. Full article
Open AccessArticle
A Privacy-Preserving Authentication and Key Agreement Scheme with Deniability for IoT
Electronics 2019, 8(4), 450; https://doi.org/10.3390/electronics8040450 (registering DOI) -
Abstract
User authentication for the Internet of Things (IoT) is a vital measure as it consists of numerous unattended connected devices and sensors. For security, only the user authenticated by the gateway node can access the real-time data gathered by sensor nodes. In this [...] Read more.
User authentication for the Internet of Things (IoT) is a vital measure as it consists of numerous unattended connected devices and sensors. For security, only the user authenticated by the gateway node can access the real-time data gathered by sensor nodes. In this article, an efficient privacy-preserving authentication and key agreement scheme for IoT is developed which enables the user, the gateway node and sensor nodes to authenticate with each other. Only the trusted gateway node can determine the real identity of user; however, no other entities can get information about user’ identity by just intercepting all exchanged messages during authentication phase. The gateway cannot prove the received messages from the sender to a third party, and thus preserving the privacy of the sender. The correctness of the proposed scheme is proved to be feasible by using BAN logic, and its security is proved under the random oracle model. The execution time of the proposed scheme is evaluated and compared with existing similar schemes, and the results demonstrate that our proposed scheme is more efficient and applicable for IoT applications. Full article
Open AccessArticle
Understanding the Unique Role of Phospholipids in the Lubrication of Natural Joints: An Interfacial Tension Study
Coatings 2019, 9(4), 264; https://doi.org/10.3390/coatings9040264 (registering DOI) -
Abstract
Some solid lubricants are characterized by a layered structure with weak (van der Waals) inter-interlayer forces which allow for easy, low-strength shearing. Solid lubricants in natural lubrication are characterized by phospholipid bilayers in the articular joints and phospholipid lamellar phases in synovial fluid. [...] Read more.
Some solid lubricants are characterized by a layered structure with weak (van der Waals) inter-interlayer forces which allow for easy, low-strength shearing. Solid lubricants in natural lubrication are characterized by phospholipid bilayers in the articular joints and phospholipid lamellar phases in synovial fluid. The influence of the acid–base properties of the phospholipid bilayer on the wettability and properties of the surface have been explained by studying the interfacial tension of spherical lipid bilayers based on a model membrane. In this paper, we show that the phospholipid multi-bilayer can act as an effective solid lubricant in every aspect, ranging from a ‘corrosion inhibitor’ in the stomach to a load-bearing lubricant in bovine joints. We present evidence of the outstanding performance of phospholipids and argue that this is due to their chemical inertness and hydrophilic–hydrophobic structure, which makes them amphoteric and provides them with the ability to form lamellar structures that can facilitate functional sliding. Moreover, the friction coefficient can significantly change for a given phospholipid bilayer so it leads to a lamellar-repulsive mechanism under highly charged conditions. After this, it is quickly transformed to result in stable low-friction conditions. Full article
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Open AccessArticle
Reliability of Fronto–Amygdala Coupling during Emotional Face Processing
Brain Sci. 2019, 9(4), 89; https://doi.org/10.3390/brainsci9040089 (registering DOI) -
Abstract
One of the most exciting translational prospects for brain imaging research is the potential use of functional magnetic resonance imaging (fMRI) ‘biomarkers’ to predict an individual’s risk of developing a neuropsychiatric disorder or the likelihood of responding to a particular intervention. This proposal [...] Read more.
One of the most exciting translational prospects for brain imaging research is the potential use of functional magnetic resonance imaging (fMRI) ‘biomarkers’ to predict an individual’s risk of developing a neuropsychiatric disorder or the likelihood of responding to a particular intervention. This proposal depends critically on reliable measurements at the level of the individual. Several previous studies have reported relatively poor reliability of amygdala activation during emotional face processing, a key putative fMRI ‘biomarker’. However, the reliability of amygdala connectivity measures is much less well understood. Here, we assessed the reliability of task-modulated coupling between three seed regions (left and right amygdala and the subgenual anterior cingulate cortex) and the dorsomedial frontal/cingulate cortex (DMFC), measured using a psychophysiological interaction analysis in 29 healthy individuals scanned approximately two weeks apart. We performed two runs on each day of three different emotional face-processing tasks: emotion identification, emotion matching, and gender classification. We tested both between-day reliability and within-day (between-run) reliability. We found good-to-excellent within-subject reliability of amygdala–DMFC coupling, both between days (in two tasks), and within day (in one task). This suggests that disorder-relevant regional coupling may be sufficiently reliable to be used as a predictor of treatment response or clinical risk in future clinical studies. Full article
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Open AccessArticle
Plant Species Recognition Skills in Finnish Students and Teachers
Educ. Sci. 2019, 9(2), 85; https://doi.org/10.3390/educsci9020085 (registering DOI) -
Abstract
Limited awareness about nature and its species can have a negative influence on children’s relationship to nature. Plant species recognition and outdoor education are perhaps the easiest way to approach nature relationships and increase knowledge. Unfortunately, it has been shown that people do [...] Read more.
Limited awareness about nature and its species can have a negative influence on children’s relationship to nature. Plant species recognition and outdoor education are perhaps the easiest way to approach nature relationships and increase knowledge. Unfortunately, it has been shown that people do not recognize plant species very well. This phenomenon is called “plant blindness”. This study presents information about the phenomenon in Finland. The purpose of this research was to determine how well Finnish students from different age groups recognize plant species and which variables explain recognition of plant species in general education in Finland. The subjects were pupils from primary school to university teachers. A total of 754 people took part in the research. The results showed that Finnish pupils do not recognize plant species very well, with wide variations in responses between student levels. Species recognition skills improved from primary school to university teachers. Full article
Open AccessReview
The Top-Viewed Cryosphere Videos on YouTube: An Overview
Geosciences 2019, 9(4), 181; https://doi.org/10.3390/geosciences9040181 (registering DOI) -
Abstract
Youtube.com has become one of the most popular places to share videos on the Internet, storing a large amount of audiovisual materials. People all over the world can upload their videos and watch videos of others. The research potential of this information source [...] Read more.
Youtube.com has become one of the most popular places to share videos on the Internet, storing a large amount of audiovisual materials. People all over the world can upload their videos and watch videos of others. The research potential of this information source has received increasing popularity across scientific disciplines. In this contribution, we explore the top viewed videos containing selected cryospheric keywords, both general (cryosphere, glacier, ice, permafrost, snow), and specific, focusing on different types of cryospheric hazards (avalanche, blizzard and glacial lake outburst flood/jokulhlaup). Searching 100 top-viewed videos for each keyword, our database consists of 859 videos. Each video is described by several qualitative characteristics (e.g., video type, geographical focus) as well as quantitative characteristics (e.g., views per day, likes). A total of 310 videos in our database (36.1% of all) are classified as videos with factual cryospheric content. We show that the broader audience represented by YouTube users is particularly interested in videos capturing dynamic processes such as calving of glaciers. While videos found for general cryosphere keywords have attracted a generally higher attention of YouTube users (total views), videos found for specific keywords are ranked among the most liked. Further, we analyze where the videos with cryospheric content are filmed, revealing several hotspots for different keywords located in all continents except for Africa. Finally, we discuss the potentials of cryosphere videos for educational and research purposes, pointing out that videos filmed by incidental witnesses of low-frequency processes such as glacial lake outburst floods might contribute to the elucidation of their dynamics, magnitude and behavior as well as the occurrence in space and time. Full article
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