MPTP-Treated Zebrafish Recapitulate ‘Late-Stage’ Parkinson’s-like Cognitive Decline

The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-µg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: The experiments were implemented using the equipment and unique scientific installation “Biological collection–Genetic biomodels of neuropsychiatric disorders” (No. 493387) of the Federal State Budgetary Scientific Institution “Scientific Research Institute of Neurosciences and Medicine” theme no. AAAA-A21-121011990039-2 (2021–2025). The study partially used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684)

Performance Scalability of the Multimedia Instruction Set Extensions

Abstract. Current media ISA extensions such as Sun’s VIS consist of SIMD-like instructions that operate on short vector registers. In order to exploit more parallelism in a superscalar processor provided with such instructions, the issue width has to be increased. In the ComplexStreamed Instruction (CSI) set exploiting more parallelism does not involve issuing more instructions. In this paper we study how the performance of superscalar processors extended with CSI or VIS scales with the amount of parallel execution hardware. Results show that the performance of the CSI-enhanced processor scales very well. For example, increasing the datapath width of the CSI execution unit from 16 to 32 bytes improves the kernel-level performance by a factor of 1.56 on average. The VISenhanced machine is unable to utilize large amounts of parallel execution hardware efficiently. Due to the huge number of instructions that need to be executed, the decode-issue logic constitutes a bottleneck.

Porting GCC to Exposed Pipeline VLIW Processors

EVP and TriMedia are embedded application processors targeted at mobile communication and multimedia domains. Both architectures originate from Philips Semiconductors and are currently developed by ST-Ericsson and NXP Semiconductors, respectively. Both processors have a VLIWarchitecture with an exposed pipeline. Such architectures impose different requirements on a compiler than the majority of existing GCC targets, which are scalar or superscalar machines with interlocked pipelines. First, the exposed pipeline organization requires a compiler to schedule operations such that all data and resource hazards are avoided. Second, a compiler for a VLIW machine has to provide stronger capabilities for discovering and exposing the instruction level parallelism (ILP), as it can not rely on the hardware ILP mechanisms employed in superscalar processors. We have ported GCC to EVP and TriMedia and provided extensions to support code generation for an exposed pipeline VLIW. To increase the amount of exploitable ILP, we have also enhanced the current GCC mechanisms such as loop unrolling and the alias analysis. The ports were benchmarked against the existing production compilers and encouraging results in terms of cycle counts and code size have been achieved.Computer EngineeringElectrical Engineering, Mathematics and Computer Scienc

Alkyl triphenylphosphonium surfactants as nucleic acid carriers: complexation efficacy toward DNA decamers, interaction with lipid bilayers and cytotoxicity studies

Herein, for the first time the complexation ability of a homological series of triphenylphosphonium surfactants (TPPB-n) toward DNA decamers has been explored. Formation of lipoplexes was confirmed by alternative techniques, including dynamic light scattering, indicating the occurrence of nanosized complexes (ca. 100-150 nm), and monitoring the charge neutralization of nucleotide phosphate groups and the fluorescence quenching of dye-intercalator ethidium bromide. The complexation efficacy of TPPB-surfactants toward an oligonucleotide (ONu) is compared with that of reference cationic surfactants. Strong effects of the alkyl chain length and the structure of the head group on the surfactant/ONu interaction are revealed, which probably occur via different mechanisms, with electrostatic and hydrophobic forces or intercalation imbedding involved. Phosphonium surfactants are shown to be capable of disordering lipid bilayers, which is supported by a decrease in the temperature of the main phase transition, Tm. This effect enhances with an increase in the alkyl chain length, indicating the integration of TPPB-n with lipid membranes. This markedly differs from the behavior of typical cationic surfactant cetyltrimethylammonium bromide, which induces an increase in the Tm value. It was demonstrated that the cytotoxicity of TPPB-n in terms of the MTT-test on a human cell line 293T nonmonotonically changes within the homological series, with the highest cytotoxicity exhibited by the dodecyl and tetradecyl homologs

Alkyl triphenylphosphonium surfactants as nucleic acid carriers: complexation efficacy toward DNA decamers, interaction with lipid bilayers and cytotoxicity studies

Herein, for the first time the complexation ability of a homological series of triphenylphosphonium surfactants (TPPB-n) toward DNA decamers has been explored. Formation of lipoplexes was confirmed by alternative techniques, including dynamic light scattering, indicating the occurrence of nanosized complexes (ca. 100-150 nm), and monitoring the charge neutralization of nucleotide phosphate groups and the fluorescence quenching of dye-intercalator ethidium bromide. The complexation efficacy of TPPB-surfactants toward an oligonucleotide (ONu) is compared with that of reference cationic surfactants. Strong effects of the alkyl chain length and the structure of the head group on the surfactant/ONu interaction are revealed, which probably occur via different mechanisms, with electrostatic and hydrophobic forces or intercalation imbedding involved. Phosphonium surfactants are shown to be capable of disordering lipid bilayers, which is supported by a decrease in the temperature of the main phase transition, Tm. This effect enhances with an increase in the alkyl chain length, indicating the integration of TPPB-n with lipid membranes. This markedly differs from the behavior of typical cationic surfactant cetyltrimethylammonium bromide, which induces an increase in the Tm value. It was demonstrated that the cytotoxicity of TPPB-n in terms of the MTT-test on a human cell line 293T nonmonotonically changes within the homological series, with the highest cytotoxicity exhibited by the dodecyl and tetradecyl homologs