Regulation of Ubiquitination-Mediated Protein Degradation by Survival Kinases in Cancer

The ubiquitin–proteasome system is essential for multiple physiological processes via selective degradation of target proteins and has been shown to plays a critical role in human cancer. Activation of oncogenic factors and inhibition of tumor suppressors have been shown to be essential for cancer development, and protein ubiquitination has been linked to the regulation of oncogenic factors and tumor suppressors. Three kinases, AKT, extracellular signal-regulated kinase, and IκB kinase, we refer to as oncokinases, are activated in multiple human cancers. We and others have identified several key downstream targets that are commonly regulated by these oncokinases, some of which are regulated directly or indirectly via ubiquitin-mediated proteasome degradation, including FOXO3, β-catenin, myeloid cell leukemia-1, and Snail. In this review, we summarize these findings from our and other groups and discuss potential future studies and applications in the clinic

ACUTE EFFECT OF VIBRATORY STIMULATION ON ELBOW JOINT FLEXOR PERFORMANCE

A novel design of vibratory stimulation training system was developed in this study. Each participant took a pre-test, before receiving treatment with 20 seconds of vibratory stimulation (VS) at a specific frequency and amplitude. The participants then took a post-test. Percentage improvement was then calculated by comparing the pre- and post-test values for each index. The experimental data were analyzed through a two-way repeated-measures ANOVA analysis, with the independent variables being vibratory frequency and amplitude and the dependent variables being EMG root mean square, maximal force, rate of force development, and average force. The optimal vibratory stimulation pattern was found from this study that being a 60% maximal force loading combined with VS at 2.5 Hz and 1 N amplitude sustained over 20 s

Prospectus, January 25, 1989

https://spark.parkland.edu/prospectus_1989/1000/thumbnail.jp

The catalytic core of DEMETER guides active DNA demethylation in Arabidopsis.

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it is recruited to these differing chromatin landscapes is unknown. The C-terminal half of DME consists of 3 conserved regions required for catalysis in vitro. We show that this catalytic core guides active demethylation at endogenous targets, rescuing dme developmental and genomic hypermethylation phenotypes. However, without the N terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. Comparative analysis revealed that the conserved DME N-terminal domains are present only in flowering plants, whereas the domain architecture of DME-like proteins in nonvascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets

Reliability and Validity of Instruments for Assessing Perinatal Depression in African Settings: Systematic Review and Meta-Analysis

Background: A major barrier to improving perinatal mental health in Africa is the lack of locally validated tools for identifying probable cases of perinatal depression or for measuring changes in depression symptom severity. We systematically reviewed the evidence on the reliability and validity of instruments to assess perinatal depression in African settings. Methods and Findings: Of 1,027 records identified through searching 7 electronic databases, we reviewed 126 full-text reports. We included 25 unique studies, which were disseminated in 26 journal articles and 1 doctoral dissertation. These enrolled 12,544 women living in nine different North and sub-Saharan African countries. Only three studies (12%) used instruments developed specifically for use in a given cultural setting. Most studies provided evidence of criterion-related validity (20 [80%]) or reliability (15 [60%]), while fewer studies provided evidence of construct validity, content validity, or internal structure. The Edinburgh postnatal depression scale (EPDS), assessed in 16 studies (64%), was the most frequently used instrument in our sample. Ten studies estimated the internal consistency of the EPDS (median estimated coefficient alpha, 0.84; interquartile range, 0.71-0.87). For the 14 studies that estimated sensitivity and specificity for the EPDS, we constructed 2 x 2 tables for each cut-off score. Using a bivariate random-effects model, we estimated a pooled sensitivity of 0.94 (95% confidence interval [CI], 0.68-0.99) and a pooled specificity of 0.77 (95% CI, 0.59-0.88) at a cut-off score of ≥9, with higher cut-off scores yielding greater specificity at the cost of lower sensitivity. Conclusions: The EPDS can reliably and validly measure perinatal depression symptom severity or screen for probable postnatal depression in African countries, but more validation studies on other instruments are needed. In addition, more qualitative research is needed to adequately characterize local understandings of perinatal depression-like syndromes in different African contexts

Towards a Tangible Blocky Coding Design for Visually Impaired Children

This paper investigates the role of coding in children\u27s education and the barriers to inclusion for Visually Impaired (VI) children in this environment. In the learning process, these children face numerous challenges, including the fact that most playful coding-related learning options rely on visualization. This paper incorporates insights from a literature review to design a solution involving a model called DODO through computer vision and tangible paper blocky modules for VI children to learn to code. The main result is the proof of concept prototype demonstrates that the proposed design can recognize the various paper modules used to represent different codes, targeting the tactile sense. The design advocates for VI children to have access to economic Science, Technology, Engineering, and Mathematics (STEM) learning

An HD domain phosphohydrolase active site tailored for oxetanocin-A biosynthesis

HD domain phosphohydrolase enzymes are characterized by a conserved set of histidine and aspartate residues that coordinate an active site metallocenter. Despite the important roles these enzymes play in nucleotide metabolism and signal transduction, few have been both biochemically and structurally characterized. Here, we present X-ray crystal structures and biochemical characterization of the Bacillus megaterium HD domain phosphohydrolase OxsA, involved in the biosynthesis of the antitumor, antiviral, and antibacterial compound oxetanocin-A. These studies reveal a previously uncharacterized reaction for this family; OxsA catalyzes the conversion of a triphosphorylated compound into a nucleoside, releasing one molecule of inorganic phosphate at a time. Remarkably, this functionality is a result of the OxsA active site, which based on structural and kinetic analyses has been tailored to bind the small, four-membered ring of oxetanocin-A over larger substrates. Furthermore, our OxsA structures show an active site that switches from a dinuclear to a mononuclear metal center as phosphates are eliminated from substrate.United States. National Institutes of Health (F32-GM108189

Metrology Camera System of Prime Focus Spectrograph for Subaru Telescope

The Prime Focus Spectrograph (PFS) is a new optical/near-infrared multi-fiber spectrograph designed for the prime focus of the 8.2m Subaru telescope. The metrology camera system of PFS serves as the optical encoder of the COBRA fiber motors for the configuring of fibers. The 380mm diameter aperture metrology camera will locate at the Cassegrain focus of Subaru telescope to cover the whole focal plane with one 50M pixel Canon CMOS sensor. The metrology camera is designed to provide the fiber position information within 5{\mu}m error over the 45cm focal plane. The positions of all fibers can be obtained within 1s after the exposure is finished. This enables the overall fiber configuration to be less than 2 minutes.Comment: 10 pages, 12 figures, SPIE Astronomical Telescopes and Instrumentation 201

Prospectus, February 15, 1989

https://spark.parkland.edu/prospectus_1989/1002/thumbnail.jp