The ubiquitin–proteasome pathway plays an important role in the pathogenesis of neurodegeneration, but mechanisms controlling expression of components in this pathway remain poorly understood. Nuclear factor E2-related factor 1 (Nrf1) transcription factor has been shown to regulate expression of antioxidant and cytoprotective genes. To determine the function of Nrf1 in the brain, mice with a late-stage deletion of
Nrf1
in neuronal cells were generated. Loss of Nrf1 leads to impaired proteasome function and neurodegeneration. Gene expression profiling and RT-PCR analysis revealed a coordinate down-regulation of various proteasomal genes including
PsmB6
, which encodes a catalytic subunit of the proteasome. Transcriptional analysis and chromatin immunoprecipitation experiments demonstrated that PsmB6 is an Nrf1 target gene. These findings reveal Nrf1 as a key transcriptional regulator required for the expression of proteasomal genes in neurons and suggest that perturbations of Nrf1 function may contribute to the pathogenesis of neurodegenerative diseases.
Pulsed coulometric detection (PCD) and potential-sweep pulsed coulometric detection (PS-PCD) are applied to the direct detection of amino acids in protein hydrolyzates. The detection mechanisms are based upon surface-catalyzed oxidation of the amine functionalities activated by the transient formation of surface oxide on Au electrodes. PCD uses a triple-step potential waveform in which the integration of electrode current at a constant potential is followed by anodic and cathodic polarizations to clean and reactivate the electrode surface. PS-PCD incorporates a cyclic potential sweep into the triple-step waveform which proceeds through the formation and subsequent removal of the surface oxide with simultaneous current integration. Reactions catalyzed by the formation of the noble metal oxide can be monitored in PS-PCD with the automatic rejection of the surface oxide background. A significant decrease is obtained also in the fluctuation and drift in the base line resulting from gradient elution and variations of the electrode surface. PCD and PS-PCD following gradient elution chromatography are demonstrated to allow for the direct detection of 20 amino acids including secondary amino acids. Detection limits for lysine are ca. 220 ppb (11 ng, 75 pmol) by PCD and 60 ppb (3 ng, 19 pmol) by PS-PCD applied at gold electrodes.
We examined a new Li-ion battery system based on the combination of a high voltage LiMn0.8Fe0.2PO4 (LMFP) cathode with a Li4Ti5O12 (LTO) anode. Due to the relatively high red-ox voltage of LTO (1.5 V vs. Li) and the excellent stability of its spinel structure, as well as the fact that the red-ox potential of a Li[MnFe]PO4 cathode, up to 4.1 V, does not endanger the anodic stability of a standard electrolyte solutions, it is assumed that such cells can be safe, stable, highly reversible, and suitable for load-leveling applications. The LMFP/LTO cells exhibited excellent rate capability and cycle life at 30°C, delivering discharge capacity of 153, 152, 146, and 118 mAhg−1 (cathode) at 0.1 C, C, 2 C, and 5 C rates. These cells demonstrated excellent high temperature performance when the LTO anodes were pre-passivated before cell operation. By XRD and ICP analyzes of C-LiMn0.8Fe0.2PO4 electrodes before and after charge/discharge cycles, the capacity fading of these systems at high temperatures was attributed to depletion of active Li from the electrodes, due to side reactions on the anode side. These were avoided by pre-passivation of the LTO electrodes. The surface chemistry of Li4Ti5O12 anodes was investigated with the anodic surface reactions arising mainly from the salt (LiPF6).
Lack of resources and exposure to neuroscience in K-12 education has resulted in a limited number of K-12 students pursuing higher education in the field. Meanwhile, the rapid expansion of the field of neuroscience has encouraged many higher educational institutes to offer neuroscience majors. This has opened up the opportunity to engage faculty, as well as graduate and undergraduate students in bringing the most needed knowledge and awareness about neuroscience into K-12 classrooms.However, undergraduate neuroscience curricula have limited formal opportunities to engage in outreach, and few existing programs have assessments to determine their effectiveness. To address these needs, we developed quantitative assessment tools that complement an existing neuroscience outreach program-Project Brainstormat the University of California, Los Angeles (UCLA). 29 UCLA undergraduates enrolled in the 2016 and 2017 programs participated in this study, along with 298 K-12 students from local schools across the Los Angeles area. In undergraduate students, we assessed (a) improvement in students' teaching/communication abilities across the course of the outreach program, and (b) confidence in explaining neuroscience topics and interest in pursuing teaching career. In K-12 students, we evaluated (a) knowledge gain in neuroscience topics and (b) interest in pursuing higher education.Overall, Project Brainstorm showed significant improvement in all the
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