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43 pages, 521 KB  
Article
On Finite Exceptional Orthogonal Polynomial Sequences Composed of Rational Darboux Transforms of Romanovski-Jacobi Polynomials
by Gregory Natanson
Axioms 2025, 14(3), 218; https://doi.org/10.3390/axioms14030218 - 16 Mar 2025
Cited by 2 | Viewed by 958
Abstract
The paper presents the united analysis of the finite exceptional orthogonal polynomial (EOP) sequences composed of rational Darboux transforms of Romanovski-Jacobi polynomials. It is shown that there are four distinguished exceptional differential polynomial systems (X-Jacobi DPSs) of series J1, J2, J3, and W. [...] Read more.
The paper presents the united analysis of the finite exceptional orthogonal polynomial (EOP) sequences composed of rational Darboux transforms of Romanovski-Jacobi polynomials. It is shown that there are four distinguished exceptional differential polynomial systems (X-Jacobi DPSs) of series J1, J2, J3, and W. The first three X-DPSs formed by pseudo-Wronskians of two Jacobi polynomials contain both exceptional orthogonal polynomial systems (X-Jacobi OPSs) on the interval (−1, +1) and the finite EOP sequences on the positive interval (1, ∞). On the contrary, the X-DPS of series W formed by Wronskians of two Jacobi polynomials contains only (infinitely many) finite EOP sequences on the interval (1, ∞). In addition, the paper rigorously examines the three isospectral families of the associated Liouville potentials (rationally extended hyperbolic Pöschl-Teller potentials of types a, b, and a) exactly quantized by the EOPs in question. Full article
21 pages, 1040 KB  
Article
AIDS-Based Cyber Threat Detection Framework for Secure Cloud-Native Microservices
by Heeji Park, Abir EL Azzaoui and Jong Hyuk Park
Electronics 2025, 14(2), 229; https://doi.org/10.3390/electronics14020229 - 8 Jan 2025
Cited by 9 | Viewed by 4307
Abstract
Cloud-native architectures continue to redefine application development and deployment by offering enhanced scalability, performance, and resource efficiency. However, they present significant security challenges, particularly in securing inter-container communication and mitigating Distributed Denial of Service (DDoS) attacks in containerized microservices. This study proposes an [...] Read more.
Cloud-native architectures continue to redefine application development and deployment by offering enhanced scalability, performance, and resource efficiency. However, they present significant security challenges, particularly in securing inter-container communication and mitigating Distributed Denial of Service (DDoS) attacks in containerized microservices. This study proposes an Artificial Intelligence Intrusion Detection System (AIDS)-based cyber threat detection solution to address these critical security challenges inherent in cloud-native environments. By leveraging a Resilient Backpropagation Neural Network (RBN), the proposed solution enhances system security and resilience by effectively detecting and mitigating DDoS attacks in real time in both the network and application layers. The solution incorporates an Inter-Container Communication Bridge (ICCB) to ensure secure communication between containers. It also employs advanced technologies such as eXpress Data Path (XDP) and the Extended Berkeley Packet Filter (eBPF) for high-performance and low-latency security enforcement, thereby overcoming the limitations of existing research. This approach provides robust protection against evolving security threats while maintaining the dynamic scalability and efficiency of cloud-native architectures. Furthermore, the system enhances operational continuity through proactive monitoring and dynamic adaptability, ensuring effective protection against evolving threats while preserving the inherent scalability and efficiency of cloud-native environments. Full article
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44 pages, 3458 KB  
Review
Network Data Plane Programming Languages: A Survey
by Belén Brandino and Eduardo Grampín
Computers 2024, 13(12), 314; https://doi.org/10.3390/computers13120314 - 26 Nov 2024
Cited by 2 | Viewed by 3962
Abstract
Network data plane programming is a consequence of the evolution of the concept of control and data plane separation, stated two decades ago, and established on the Software-Defined Networking (SDN) architecture. The concept has been evolving since its initial implementation using the OpenFlow [...] Read more.
Network data plane programming is a consequence of the evolution of the concept of control and data plane separation, stated two decades ago, and established on the Software-Defined Networking (SDN) architecture. The concept has been evolving since its initial implementation using the OpenFlow protocol, whereby an omniscient external entity, the controller, dynamically configures the forwarding of network devices, which are basically “dummies”. In this paper, we review network data plane programming languages, describing their theoretical characteristics and presenting examples and possible targets in order to compare them, in search of the best solutions to have a network of dynamically programmable devices that allow the network operator to deploy innovative use cases without depending on the manufacturer, promoting innovation. The main contribution is to gather in one place the existing languages, present them, and compare different features to help the operator and programmers. Overall, we conclude that today, the language with the most development and device targets is P4, although there are many developments based on XDP and eBPF that can be useful when implementing a programmable network solution. Full article
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16 pages, 2714 KB  
Article
Apolar Extracts of St. John’s Wort Alleviate the Effects of β-Amyloid Toxicity in Early Alzheimer’s Disease
by Ahmed El Menuawy, Thomas Brüning, Iván Eiriz, Urs Hähnel, Frank Marthe, Luisa Möhle, Anna Maria Górska, Irene Santos-García, Helle Wangensteen, Jingyun Wu and Jens Pahnke
Int. J. Mol. Sci. 2024, 25(2), 1301; https://doi.org/10.3390/ijms25021301 - 21 Jan 2024
Cited by 7 | Viewed by 4198
Abstract
Hypericum perforatum (St. John’s wort) has been described to be beneficial for the treatment of Alzheimer’s disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. [...] Read more.
Hypericum perforatum (St. John’s wort) has been described to be beneficial for the treatment of Alzheimer’s disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral β-amyloid (Aβ) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aβ were analyzed using biochemical analyses. Our study confirms that the scCO2H. perforatum formulation shows better biological activity against Aβ-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aβ (−27% and −25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD. Full article
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19 pages, 2824 KB  
Protocol
Design of Fault-Tolerant Automotive Gateway Architecture Using MC9S12XDP512 Microcontroller Device
by Ramesh Krishnamoorthy, Bharatiraja Chokkalingam and Josiah Lange Munda
Energies 2023, 16(16), 5923; https://doi.org/10.3390/en16165923 - 10 Aug 2023
Cited by 3 | Viewed by 3651
Abstract
The increasing number of electrical components and sensors in modern vehicles makes network design more challenging. The development of automotive electronics through multiple communication protocols brings out the importance of a hybrid network that is both optimal and fault-tolerant. In order for a [...] Read more.
The increasing number of electrical components and sensors in modern vehicles makes network design more challenging. The development of automotive electronics through multiple communication protocols brings out the importance of a hybrid network that is both optimal and fault-tolerant. In order for a vehicle to communicate with electronic components like engine management systems, stability control units, braking systems, and door functions, a CAN (controller area network) is developed. In order to create a hierarchical vehicle network gateway for quality fortification and cost reduction of vehicles, the CAN and LIN (local interconnect network) are considered. This standardisation will reduce the variety of low-end multiplex solutions currently available for automotive electronics’ development costs, production rates, service fees, and logistics costs. The implementation of a gateway in these electronic devices is made possible with the proposed hybrid architecture. This system effectively shows the high-speed and low-speed applications relevant to crucial ECUs in the network by using two distinct CAN and LIN gateways to send sensor data between the ECUs (electronic control units). Full article
(This article belongs to the Section A: Sustainable Energy)
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15 pages, 4020 KB  
Article
Detection of Denial of Service Attack in Cloud Based Kubernetes Using eBPF
by Amin Sadiq, Hassan Jamil Syed, Asad Ahmed Ansari, Ashraf Osman Ibrahim, Manar Alohaly and Muna Elsadig
Appl. Sci. 2023, 13(8), 4700; https://doi.org/10.3390/app13084700 - 7 Apr 2023
Cited by 15 | Viewed by 6574
Abstract
Kubernetes is an orchestration tool that runs and manages container-based workloads. It works as a collection of different virtual or physical servers that support multiple storage capacities, provide network functionalities, and keep all containerized applications active in a desired state. It also provides [...] Read more.
Kubernetes is an orchestration tool that runs and manages container-based workloads. It works as a collection of different virtual or physical servers that support multiple storage capacities, provide network functionalities, and keep all containerized applications active in a desired state. It also provides an increasing fleet of different facilities, known as microservices. However, Kubernetes’ scalability has led to a complex network structure with an increased attack vector. Attackers can launch a Denial of service (DoS) attack against servers/machines in Kubernetes by producing fake traffic load, for instance. DoS or Distributed Denial of service (DDoS) attacks are malicious attempts to disrupt a targeted service by flooding the target’s service with network packets. Constant observation of the network traffic is extremely important for the early detection of such attacks. Extended Berkeley Packet Filter (eBPF) and eXpress Datapath (XDP) are advanced technologies in the Linux kernel that perform high-speed packet processing. In the case of Kubernetes, eBPF and XDP can be used to protect against DDoS attacks by enabling fast and efficient network security policies. For example, XDP can be used to filter out traffic that is not authorized to access the Kubernetes cluster, while eBPF can be used to monitor network traffic for signs of DDoS attacks, such as excessive traffic from a single source. In this research, we utilize eBPF and XDP to build a detection and observation mechanism to filter out malicious content and mitigate a Denial of Service attack on Kubernetes. Full article
(This article belongs to the Special Issue Edge and Cloud Computing Systems and Applications)
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15 pages, 2192 KB  
Article
Development of 3D Printed Multi-Layered Orodispersible Films with Porous Structure Applicable as a Substrate for Inkjet Printing
by Jan Elbl, Martin Veselý, Dagmar Blaháčková, Jaroslav Ondruš, Pavel Kulich, Eliška Mašková, Josef Mašek and Jan Gajdziok
Pharmaceutics 2023, 15(2), 714; https://doi.org/10.3390/pharmaceutics15020714 - 20 Feb 2023
Cited by 18 | Viewed by 4565
Abstract
The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for [...] Read more.
The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for medicated ink deposited by a 2D printer. The innovative semi-solid extrusion 3D printing method was employed to produce multilayered ODFs, where the bottom layer assures the mechanical properties. In contrast, the top layer provides a porous structure for ink entrapment. Hydroxypropyl methylcellulose and polyvinyl alcohol were utilized as film-forming polymers, glycerol as a plasticizer, and sodium starch glycolate as a disintegrant in the bottom matrix. Several porogen agents (Aeroperl® 300, Fujisil®, Syloid® 244 FP, Syloid® XDP 3050, Neusilin® S2, Neusilin® US2, and Neusilin® UFL2) acted as porosity enhancers in the two types of top layer. ODFs with satisfactory disintegration time were prepared. The correlation between the porogen content and the mechanical properties was proved. A porous ODF structure was detected in most samples and linked to the porogen content. SSE 3D printing represents a promising preparation method for the production of porous ODFs as substrates for subsequent drug deposition by 2D printing, avoiding the difficulties arising in casting or printing medicated ODFs directly. Full article
(This article belongs to the Special Issue 3D Printing Technology for Pharmaceutical and Biomedical Application)
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13 pages, 5516 KB  
Article
RETRACTED: Express Data Processing on FPGA: Network Interface Cards for Streamlined Software Inspection for Packet Processing
by Sunkari Pradeep, Yogesh Kumar Sharma, Chaman Verma, Gutha Sreeram and Panugati Hanumantha Rao
Appl. Syst. Innov. 2023, 6(1), 9; https://doi.org/10.3390/asi6010009 - 9 Jan 2023
Cited by 1 | Viewed by 4163 | Retraction
Abstract
Modern computers’ network interface cards (NICs) are undergoing changes in order to handle greater data rates and assist with scaling problems caused by general-purpose CPU technology. The inclusion of programmable accelerators to the NIC’s data channel is one of the ongoing improvements that [...] Read more.
Modern computers’ network interface cards (NICs) are undergoing changes in order to handle greater data rates and assist with scaling problems caused by general-purpose CPU technology. The inclusion of programmable accelerators to the NIC’s data channel is one of the ongoing improvements that is particularly intriguing since it gives the accelerator the chance to take on a portion of the CPU’s network packet processing duties. Accelerators are frequently developed using platforms like field-programmable gate arrays because packet processing operations have severe latency requirements (FPGAs). When implementing packet processing activities, FPGAs’ gain for through put is the number of data packets being successfully sent per second and latency is the actual time those packets take. However, due to their restricted resources, programming may need to be shared throughout a variety of applications. We provide hXDP, a software solution for FPGAs that targets the Linux eXpress Data Path and performs packet processing functions outlined with the eBPF technology. While maintaining performance on par with top-tier CPUs, hXDP only uses a tiny portion from the field programmable gate arrays, which are semiconductor devices that are based around a matrix of configuration logic blocks (CLB) connected over programmable interconnects. However, we demonstrate that when aiming towards a purpose-built FPGA architecture, many extended Berkeley packet filters (eBPF) allow programmers to use Berkeley packet filter byte code that makes use of certain kernel resources and instruction set architecture, to collocate and even eliminate, with considerably productivity and effectiveness. On an FPGA NIC, we implement hXDP and test its effectiveness using authentic eBPF programmes from the real world. Our version consumes 15% of the FPGA resources and operates at 156.25 MHz. This can constantly change and lead to the act of identification, inspection, extraction, and manipulation so that a network may make more intelligent management decisions. Full article
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19 pages, 3584 KB  
Article
Postnatal Conditional Deletion of Bcl11b in Striatal Projection Neurons Mimics the Transcriptional Signature of Huntington’s Disease
by Sicheng Song, Jordi Creus Muncunill, Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, B. Wade Hamilton, Akos A. Gerencser, Houda Benlhabib, Maria-Daniela Cirnaru, Mark Leid, Sean D. Mooney, Lisa M. Ellerby and Michelle E. Ehrlich
Biomedicines 2022, 10(10), 2377; https://doi.org/10.3390/biomedicines10102377 - 23 Sep 2022
Cited by 4 | Viewed by 3888
Abstract
The dysregulation of striatal gene expression and function is linked to multiple diseases, including Huntington’s disease (HD), Parkinson’s disease, X-linked dystonia-parkinsonism (XDP), addiction, autism, and schizophrenia. Striatal medium spiny neurons (MSNs) make up 90% of the neurons in the striatum and are critical [...] Read more.
The dysregulation of striatal gene expression and function is linked to multiple diseases, including Huntington’s disease (HD), Parkinson’s disease, X-linked dystonia-parkinsonism (XDP), addiction, autism, and schizophrenia. Striatal medium spiny neurons (MSNs) make up 90% of the neurons in the striatum and are critical to motor control. The transcription factor, Bcl11b (also known as Ctip2), is required for striatal development, but the function of Bcl11b in adult MSNs in vivo has not been investigated. We conditionally deleted Bcl11b specifically in postnatal MSNs and performed a transcriptomic and behavioral analysis on these mice. Multiple enrichment analyses showed that the D9-Cre-Bcl11btm1.1Leid transcriptional profile was similar to the HD gene expression in mouse and human data sets. A Gene Ontology enrichment analysis linked D9-Cre-Bcl11btm1.1Leid to calcium, synapse organization, specifically including the dopaminergic synapse, protein dephosphorylation, and HDAC-signaling, commonly dysregulated pathways in HD. D9-Cre-Bcl11btm1.1Leid mice had decreased DARPP-32/Ppp1r1b in MSNs and behavioral deficits, demonstrating the dysregulation of a subtype of the dopamine D2 receptor expressing MSNs. Finally, in human HD isogenic MSNs, the mislocalization of BCL11B into nuclear aggregates points to a mechanism for BCL11B loss of function in HD. Our results suggest that BCL11B is important for the function and maintenance of mature MSNs and Bcl11b loss of function drives, in part, the transcriptomic and functional changes in HD. Full article
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19 pages, 2257 KB  
Article
Effect of Sound Coding Strategies on Music Perception with a Cochlear Implant
by Gaëlle Leterme, Caroline Guigou, Geoffrey Guenser, Emmanuel Bigand and Alexis Bozorg Grayeli
J. Clin. Med. 2022, 11(15), 4425; https://doi.org/10.3390/jcm11154425 - 29 Jul 2022
Cited by 4 | Viewed by 2755
Abstract
The goal of this study was to evaluate the music perception of cochlear implantees with two different sound processing strategies. Methods: Twenty-one patients with unilateral or bilateral cochlear implants (Oticon Medical®) were included. A music trial evaluated emotions (sad versus happy [...] Read more.
The goal of this study was to evaluate the music perception of cochlear implantees with two different sound processing strategies. Methods: Twenty-one patients with unilateral or bilateral cochlear implants (Oticon Medical®) were included. A music trial evaluated emotions (sad versus happy based on tempo and/or minor versus major modes) with three tests of increasing difficulty. This was followed by a test evaluating the perception of musical dissonances (marked out of 10). A novel sound processing strategy reducing spectral distortions (CrystalisXDP, Oticon Medical) was compared to the standard strategy (main peak interleaved sampling). Each strategy was used one week before the music trial. Results: Total music score was higher with CrystalisXDP than with the standard strategy. Nine patients (21%) categorized music above the random level (>5) on test 3 only based on mode with either of the strategies. In this group, CrystalisXDP improved the performances. For dissonance detection, 17 patients (40%) scored above random level with either of the strategies. In this group, CrystalisXDP did not improve the performances. Conclusions: CrystalisXDP, which enhances spectral cues, seemed to improve the categorization of happy versus sad music. Spectral cues could participate in musical emotions in cochlear implantees and improve the quality of musical perception. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Application of Cochlear Implantation)
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18 pages, 2069 KB  
Article
Comparative Study of Powder Carriers Physical and Structural Properties
by Klára Kostelanská, Barbora Blahová Prudilová, Sylva Holešová, Jakub Vlček, David Vetchý and Jan Gajdziok
Pharmaceutics 2022, 14(4), 818; https://doi.org/10.3390/pharmaceutics14040818 - 8 Apr 2022
Cited by 25 | Viewed by 5719
Abstract
High specific surface area (SSA), porous structure, and suitable technological characteristics (flow, compressibility) predetermine powder carriers to be used in pharmaceutical technology, especially in the formulation of liquisolid systems (LSS) and solid self-emulsifying delivery systems (s-SEDDS). Besides widely used microcrystalline cellulose, other promising [...] Read more.
High specific surface area (SSA), porous structure, and suitable technological characteristics (flow, compressibility) predetermine powder carriers to be used in pharmaceutical technology, especially in the formulation of liquisolid systems (LSS) and solid self-emulsifying delivery systems (s-SEDDS). Besides widely used microcrystalline cellulose, other promising materials include magnesium aluminometasilicates, mesoporous silicates, and silica aerogels. Clay minerals with laminar or fibrous internal structures also provide suitable properties for liquid drug incorporation. This work aimed at a comparison of 14 carriers’ main properties. Cellulose derivatives, silica, silicates, and clay minerals were evaluated for flow properties, shear cell experiments, SSA, hygroscopicity, pH, particle size, and SEM. The most promising materials were magnesium aluminometasilicates, specifically Neusilin® US2, due to its proper flow, large SSA, etc. Innovative materials such as FujiSil® or Syloid® XDP 3050 were for their properties evaluated as suitable. The obtained data can help choose a suitable carrier for formulations where the liquid phase is incorporated into the solid dosage form. All measurements were conducted by the same methodology and under the same conditions, allowing a seamless comparison of property evaluation between carriers, for which available company or scientific sources do not qualify due to different measurements, conditions, instrumentation, etc. Full article
(This article belongs to the Collection Advanced Pharmaceutical Research in the Czech Republic)
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19 pages, 1965 KB  
Article
Run-Time Adaptive In-Kernel BPF/XDP Solution for 5G UPF
by Thiago A. Navarro do Amaral, Raphael V. Rosa, David F. Cruz Moura and Christian Esteve Rothenberg
Electronics 2022, 11(7), 1022; https://doi.org/10.3390/electronics11071022 - 24 Mar 2022
Cited by 10 | Viewed by 7668
Abstract
Flexibility is considered a key feature of 5G softwarization to deliver a timely response to changes in network requirements that may be caused by traffic variation, user mobility, dynamic network function chains, slice lifecycle management operations, among others. In this article, we evolve [...] Read more.
Flexibility is considered a key feature of 5G softwarization to deliver a timely response to changes in network requirements that may be caused by traffic variation, user mobility, dynamic network function chains, slice lifecycle management operations, among others. In this article, we evolve the upf-bpf1 open-source project by proposing a new design to improve its flexibility by reducing the run-time adaptation time. The project proposes an in-kernel solution based on BPF and eXpress Data Path (XDP) for 5G User Plane Function (UPF) implementations. The Just-In-Time (JIT) compilation may have a huge impact on the adaptation time due to the in-kernel verification of the BPF programs at run-time. Our results show latency improvements of around 95% to inject the BPF program into the Linux kernel. Furthermore, the solution keeps the same functionalities and delivers a packet processing performance of around 10–11 Mpps using 6 cores with almost 70% of the CPU utilization in downlink/uplink directions. Full article
(This article belongs to the Special Issue New Trends in SDN/NFV Architectures and Routing Solutions)
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14 pages, 1916 KB  
Article
Transcriptional Alterations in X-Linked Dystonia–Parkinsonism Caused by the SVA Retrotransposon
by Jelena Pozojevic, Shela Marie Algodon, Joseph Neos Cruz, Joanne Trinh, Norbert Brüggemann, Joshua Laß, Karen Grütz, Susen Schaake, Ronnie Tse, Veronica Yumiceba, Nathalie Kruse, Kristin Schulz, Varun K. A. Sreenivasan, Raymond L. Rosales, Roland Dominic G. Jamora, Cid Czarina E. Diesta, Jakob Matschke, Markus Glatzel, Philip Seibler, Kristian Händler, Aleksandar Rakovic, Henriette Kirchner, Malte Spielmann, Frank J. Kaiser, Christine Klein and Ana Westenbergeradd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(4), 2231; https://doi.org/10.3390/ijms23042231 - 17 Feb 2022
Cited by 9 | Viewed by 4727
Abstract
X-linked dystonia–parkinsonism (XDP) is a severe neurodegenerative disorder that manifests as adult-onset dystonia combined with parkinsonism. A SINE-VNTR-Alu (SVA) retrotransposon inserted in an intron of the TAF1 gene reduces its expression and alters splicing in XDP patient-derived cells. As a consequence, increased levels [...] Read more.
X-linked dystonia–parkinsonism (XDP) is a severe neurodegenerative disorder that manifests as adult-onset dystonia combined with parkinsonism. A SINE-VNTR-Alu (SVA) retrotransposon inserted in an intron of the TAF1 gene reduces its expression and alters splicing in XDP patient-derived cells. As a consequence, increased levels of the TAF1 intron retention transcript TAF1-32i can be found in XDP cells as compared to healthy controls. Here, we investigate the sequence of the deep intronic region included in this transcript and show that it is also present in cells from healthy individuals, albeit in lower amounts than in XDP cells, and that it undergoes degradation by nonsense-mediated mRNA decay. Furthermore, we investigate epigenetic marks (e.g., DNA methylation and histone modifications) present in this intronic region and the spanning sequence. Finally, we show that the SVA evinces regulatory potential, as demonstrated by its ability to repress the TAF1 promoter in vitro. Our results enable a better understanding of the disease mechanisms underlying XDP and transcriptional alterations caused by SVA retrotransposons. Full article
(This article belongs to the Special Issue Transcriptional Regulation and Its Misregulation in Human Diseases)
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12 pages, 1350 KB  
Article
Elucidating Hexanucleotide Repeat Number and Methylation within the X-Linked Dystonia-Parkinsonism (XDP)-Related SVA Retrotransposon in TAF1 with Nanopore Sequencing
by Theresa Lüth, Joshua Laβ, Susen Schaake, Inken Wohlers, Jelena Pozojevic, Roland Dominic G. Jamora, Raymond L. Rosales, Norbert Brüggemann, Gerard Saranza, Cid Czarina E. Diesta, Kathleen Schlüter, Ronnie Tse, Charles Jourdan Reyes, Max Brand, Hauke Busch, Christine Klein, Ana Westenberger and Joanne Trinh
Genes 2022, 13(1), 126; https://doi.org/10.3390/genes13010126 - 11 Jan 2022
Cited by 17 | Viewed by 4915
Abstract
Background: X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by progressive dystonia and parkinsonism. It is caused by a SINE-VNTR-Alu (SVA) retrotransposon insertion in the TAF1 gene with a polymorphic (CCCTCT)n domain that acts as a genetic modifier of [...] Read more.
Background: X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by progressive dystonia and parkinsonism. It is caused by a SINE-VNTR-Alu (SVA) retrotransposon insertion in the TAF1 gene with a polymorphic (CCCTCT)n domain that acts as a genetic modifier of disease onset and expressivity. Methods: Herein, we used Nanopore sequencing to investigate SVA genetic variability and methylation. We used blood-derived DNA from 96 XDP patients for amplicon-based deep Nanopore sequencing and validated it with fragment analysis which was performed using fluorescence-based PCR. To detect methylation from blood- and brain-derived DNA, we used a Cas9-targeted approach. Results: High concordance was observed for hexanucleotide repeat numbers detected with Nanopore sequencing and fragment analysis. Within the SVA locus, there was no difference in genetic variability other than variations of the repeat motif between patients. We detected high CpG methylation frequency (MF) of the SVA and flanking regions (mean MF = 0.94, SD = ±0.12). Our preliminary results suggest only subtle differences between the XDP patient and the control in predicted enhancer sites directly flanking the SVA locus. Conclusions: Nanopore sequencing can reliably detect SVA hexanucleotide repeat numbers, methylation and, lastly, variation in the repeat motif. Full article
(This article belongs to the Special Issue Parkinson's Disease: Genetics and Pathogenesis)
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7 pages, 4720 KB  
Case Report
Transcranial Magnetic Resonance-Guided Focused Ultrasound in X-Linked Dystonia-Parkinsonism
by Roland Dominic G. Jamora, Wei-Chieh Chang and Takaomi Taira
Life 2021, 11(5), 392; https://doi.org/10.3390/life11050392 - 26 Apr 2021
Cited by 17 | Viewed by 3564
Abstract
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative condition found among males with maternal ancestry from Panay Island, Philippines. The treatment options are limited. We report on our experience of three XDP patients who underwent transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy. The three [...] Read more.
X-linked dystonia-parkinsonism (XDP) is a neurodegenerative condition found among males with maternal ancestry from Panay Island, Philippines. The treatment options are limited. We report on our experience of three XDP patients who underwent transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) pallidothalamic tractotomy. The three patients were all genetically confirmed XDP, with a mean XDP-Movement Disorder Society of the Philippines (MDSP) Scale score of 68.7/200. All patients were on stable doses of their oral medications and their last botulinum toxin injection was 12 months prior to study. Two patients complained of moderate to severe arm pain 2–7 months after the procedure. There was an overall improvement in the XDP-MDSP Scale score of 36.2% (18.7 vs. 15) at 6 months and 30.1% (68.7 vs. 45.5) at 1 year. Notably, there was worsening of the nonmotor subscale (part IIIB, nonbehavioral aspect) by 350% at 1 year. While these numbers are encouraging, there is a need to do a larger study on the safety and efficacy of tcMRgFUS on XDP. Full article
(This article belongs to the Special Issue Dystonia and Related Disorders: From Bench to Bedside)
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